Objective: To investigate the relationship between RAS gene mutation, microsatellite instability (MSI) status and clinicopathological features and prognosis in patients with colorectal cancer. Methods: KRAS, NRAS and BRAF gene mutations and MSI status were examined in 202 patients with colorectal cancer. Statistical methods were used to analyze the relationship between gene mutations with clinicopathological features and prognosis in different groups, such as age, sex, tumor size, degree of differentiation, and so on. Results: KRAS gene mutation, BRAF gene mutation and microsatellite instability-high (MSI-H) tumor mainly occurred in the right colon with mucinous adenocarcinoma, while p53 mutation occurred more frequently in rectal tumors without mucinous adenocarcinoma. Univariate analysis showed that the progression-free survival time (PFS) of the RAS mutant in stage III CRC was significantly shorter than that of the wild type (HR: 1.804, 95%CI: 1.159 to 2.808; P=0.009). In the stage III CRC, the PFS of the double wild type group (one of the three genes KRAS, NRAS, BRAF) was significantly shorter than that of all three wild types (HR: 1.962, 95%CI: 1.254 to 3.071; P=0.003). Similarly, in multivariate analysis, both RAS and BRAF in stage III CRC were wild type, PFS was significantly longer than that in patients with any mutant type (HR: 1.962, 95%CI: 1.253 to 3.071; P=0.003). However, univariate and multivariate analysis showed that there was no significant difference in overall survival (OS) time among RAS mutation and BRAF mutation subgroups. Conclusion: RAS, BRAF mutation and MSI status can predict the prognosis of stage III and IV colorectal cancer, which need to be verified by large sample size and fine grouping.