Abstract: Objective To investigate the expression and clinical significance of melanoma nuclear protein-18 (MEL-18) and cellular myelocytomatosis oncogene (C-Myc) in cervical cancer. Methods The levels of MEL-18 and C-Myc mRNA in chronic cervicitis tissues, high-grade cervical intraepithelial neoplasia (CIN) tissues, and cervical cancer tissues were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The expression of MEL-18 and C-Myc proteins in chronic cervicitis tissues (n=30), high-grade CIN tissues (n=30), and cervical cancer tissues (n=96) was detected by immunohistochemistry. The correlation between the two proteins was analyzed, along with their relationship with the clinicopathological characteristics of cervical cancer patients. The Cox proportional hazards regression model was used to analyze prognostic factors in cervical cancer patients. Receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic value of MEL-18 and C-Myc for cervical cancer. Results With the progression of cervical lesions, the expression of MEL-18 and C-Myc gradually increased (P<0.001). MEL-18 protein expression was positively correlated with C-Myc protein expression (P<0.05). Significant differences in MEL-18 and C-Myc protein expression were observed among cervical cancer patients with different FIGO stages, degrees of differentiation, and presence or absence of lymph node metastasis (P<0.05), while no statistical differences were found among cervical cancer patients with different ages, histological types, or depth of myometrial invasion (P>0.05). The cumulative survival time of patients with positive MEL-18 and C-Myc expression was significantly shorter than that of patients with negative expression (P<0.05). FIGO stage, positive MEL-18 expression, and positive C-Myc expression were identified as independent risk factors for poor prognosis in cervical cancer. MEL-18 and C-Myc had certain diagnostic value in cervical cancer, with improved diagnostic efficiency when used in combination. Conclusions MEL-18 and C-Myc are jointly involved in the occurrence and progression of cervical cancer and influence patient prognosis.