Objective:To investigate the expression of RAD18 in colon cancer and its correlation with proliferating cell nuclear antigen (PCNA).Methods:The glass slice of colon cancer tissues and adjacent normal tissues from patients (73 cases) who underwent surgical treatment at the Second Hospital of Tianjin Medical University from November 2013 to November 2023 were collected.The expression of RAD18 in colon cancer tissues and adjacent normal tissues was analyzed in the gene expression profiling interactive analysis (GEPIA) database and verified by immunohistochemical staining. The relationship between RAD18 expression and clinicopathological features of colon cancer patients was analyzed. HCT116 and HT29 cells were cultured in vitro, and the control group and transfection group ( transfected with RAD18 shRNA to knock down RAD18 ) were set up. The expression of RAD18 was evaluated by quantitative real-time PCR (qRT-PCR) and Western Blot. The effect of RAD18 on colon cancer cell proliferation was explored using clonogenic assays and cell counting Kit-8 (CCK-8) assays. The correlation between RAD18 and PCNA was investigated by GEPIA and immunohistochemical staining. Results:The GEPIA database analysis showed that the expression of RAD18 in colon cancer tissue ( n = 275) was significantly higher than that in adjacent normal tissues ( n = 349, P < 0.05). RAD18 was expressed at higher levels in colon cancer tissue than that in adjacent normal tissues and was not expressed at high levels in the latter. The expression of RAD18 was closely related to tumor size in the low-expression group and high-expression group of patients ( P = 0.015) but was not related to age ( P = 0.115), gender ( P = 0.665), or tumor differentiation ( P = 0.733). Compared with the control group, the expressions of RAD18 in the transfection group of HCT116 and HT29 cells were both reduced (both P < 0.05). Compared with the control group, the clone cell number and absorbance ( A) value of HCT116 and HT29 cells in the transfection group were decreased (all P < 0.05). GEPIA database analysis showed that RAD18 was correlated with PCNA ( R = 0.27, P < 0.05), and the expression level of PCNA was higher in colon cancer tissues than in adjacent normal tissues. Conclusions:RAD18 is expressed at a higher level in colon cancer tissues and may promote colorectal cancer proliferation by affecting PCNA.