Abstract Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) still present a huge threaten to women’s health, especially the local advanced patients. Hence, developing more effectiveness prognostic signatures is urgently needed. This study constructed and verified a robust RNA-binding proteins (RBPs) related signature through a series of bioinformatics methods and explored the biological function of hub RBP in vitro experiments. As a result, the 10 RBPs signature was successfully established and could act as an independent prognostic biomarker in CESC patients, which displayed the highest sensitivity and specificity in prognosis prediction compared with other clinicopathological parameters. The risk model also presented good performance in risk stratification among CESC patients. Besides, a nomogram was constructed based on pathological stage and the risk signature and exhibited satisfactory accuracy in prognosis prediction. Functional enrichment indicated that the risk signature mainly participated in immune-related pathways and cancer-related pathways, and the infiltration level of immune cells and immune checkpoints showed a significantly higher degree in low-risk patients compared with high-risk patients. Notably, the 10 RBPs signature act as a novel biomarker in immunotherapy and chemotherapy response. In addition, PRPF40B was selected as hub RBP and its transcription and translation levels were obviously increased in CESC tissues, as well as Hela and Siha cells. Knockdown of PRPF40B inhibits the proliferation, migration and invasion of Hela and Siha cells in vitro. In conclusion, our research provides a noticeable strategy in prognostic prediction among CESC patients, which may illuminate the prospect of CESC patients’ clinical outcome. Supplementary Information The online version contains supplementary material available at 10.1186/s12935-024-03257-w. Keywords: RNA-binding proteins, CESC, Prognosis, Immunotherapy, Chemotherapy Introduction Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) have been the fourth leading cause of morbidity and mortality among women cancers, with approximately 604,127 (3.1%) newly incidences and 341,831 (3.4%) newly death in 2020 [[41]1]. CESC is curable in the early stage, but the locally advanced cases with or without distant metastasis usually present poor prognosis even though the combination therapeutic including surgical intervention, radiotherapy and chemotherapy have been implicated in these patients [[42]2]. Recently, emerging prevention strategies have been launched into clinical practice, including human papillomavirus (HPV) vaccine and early cervical screening, after WHO called for elimination of CESC all over the world [[43]3]. With the development of detection technology, increasingly advanced CESC has been diagnosed earlier and more accurately. Meanwhile, novel measures such as the target therapy and immunotherapy also have been applied [[44]4, [45]5]. However, limited by tumor heterogeneity and economic factors, the above treatment measures are difficult to be effectively implemented, thus, CESC is still a major threaten to poor prognosis among females, especially in the developing countries [[46]6, [47]7]. Nowadays, next-generation sequencing has been widely employed in various aspects of cancer research, and it is becoming an effective method to extensively screen biomarkers for prognosis evaluation and therapy target selection [[48]8]. Comprehensively analysis of genome transcription and multi-omics analysis could select promising biomarkers in a less expensive way, which may alleviate the nonnegligible burden generated by HPV vaccination and cytological examination [[49]9]. Therefore, discovering the novel biomarkers for CESC is urgently needed and could provide valuable information for further research. RNA binding proteins (RBPs) are proteins that interact with many types of RNA. So far, more than 1500 RBPs have been found in the human genome [[50]10]. RBPs participate in the post transcriptional regulation of RNA, determine the function of each RNA transcript in cells, and ensure cell homeostasis [[51]11]. They establish highly dynamic interactions with other proteins and coding RNA and non-coding RNA to form functional units called ribonucleoprotein complexes, which have the functions of regulating RNA splicing, polyadenylation, stability, localization, translation and degradation [[52]12]. In gynecological malignant tumors, more and more abnormally expressed RBPs have attracted people’s attention. They play an important role in the occurrence and development of tumors by influencing the proliferation, apoptosis, epithelial mesenchymal transition (EMT), invasion and metastasis, drug resistance and other processes of cancer cells [[53]13]. In the future, they may be helpful for early diagnosis or serve as a target for the treatment of tumor recurrence, so as to improve the prognosis of patients and prolong their survival time [[54]14]. In addition, RBPs may be used as diagnostic markers or potential therapeutic targets, and could participate in the proliferation, cell cycle, apoptosis, drug resistance and other related biological processes of CESC [[55]15]. Therefore, a comprehensive analysis of the biological function and prognosis of RBPs will help to better understand the occurrence and development of CESC, and may reveal new targets for therapeutic application and provide further ideas and references for subsequent research.