Objective: To investigate the influence of primary tumor resection on prognosis of patients with stage IVB colorectal cancer. Methods: A total of 6 934 patients diagnosed as stage IVB colorectal cancer between 2010 and 2013 were collected from the SEER database. Of the patients, 2 824 cases underwent primary tumor resection combined with systemic chemotherapy (surgery-chemotherapy group) and 4 110 cases underwent systemic chemotherapy alone (chemotherapy group). The difference in survival rate between the two groups of patients was compared after the clinicopathologic characteristics of the two groups of patients were balanced by propensity score matching (PSM). Results: Before PSM, the survival rate in surgery-chemotherapy group was significantly better than that in chemotherapy group (HR=1.540, 95% CI=1.423–1.667, P<0.001), but there were significant imbalances in clinicopathologic characteristics (age, gender, primary tumor site, degree of histological differentiation, T stage, N stage, metastases and CEA level) between the two groups of patients (all P<0.001). After 1:1 matching of PSM, 3 826 patients were selected with 1 913 cases in either group; the differences in clinicopathologic characteristics between the two groups of patients were markedly minimized, in which, the distributions of age, gender, primary tumor site, N stage, metastases and CEA level of the two groups were well balanced (all P>0.05); the survival rate in surgery-chemotherapy group was significantly better than that in chemotherapy group (HR=1.603, 95% CI= 1.439–1.787, P<0.001). Conclusion: Surgical resection of the primary tumor can improve the prognosis of colorectal cancer patients with unresectable metastatic lesions. So, the treatment strategy of primary tumor resection combined with systemic chemotherapy is recommended for patients with stage IVB colorectal cancer and surgical tolerance.