Abstract: Objective To investigate the expression of the colorectal cancer differentially expressed (CRNDE) gene in cervical cancer and its relationship with clinical features and prognosis of patients. Methods The expression differences of CRNDE between cervical cancer tissues and normal tissues were analyzed using online databases. The results were verified with clinical tissue samples using real-time quantitative fluorescence PCR. The relationship between CRNDE expression and clinical features of cervical cancer patients was further analyzed. Univariate and multivariate Cox regression analyses were used to assess the relationship between CRNDE expression and prognosis of cervical cancer patients. Additionally, Western blot was performed to detect changes in the expression of ERK, MEK, p-ERK, and p-MEK proteins in Hela cells after CRNDE silencing. Results CRNDE expression was significantly upregulated in cervical cancer tissues (P<0.05). The expression of CRNDE was significantly associated with the FIGO stage, histological grade, N stage, and M stage of cervical cancer (P<0.05). Patients with high CRNDE expression had a significantly shorter survival time than those with low CRNDE expression (P<0.05). The FIGO stage, histological grade, T stage, N stage, M stage, and CRNDE expression level were independent prognostic factors for the overall survival of cervical cancer patients. After CRNDE silencing, the levels of p-ERK and p-MEK were significantly downregulated in Hela cells (P<0.05). Conclusions High expression of CRNDE in cervical cancer tissues is associated with poor prognosis in cervical cancer patients. CRNDE may serve as a potential diagnostic and therapeutic target for cervical cancer by modulating the MAPK/ERK signaling pathway.