Objective: To compare the difference of efficacy and safety between the chemotherapies and the chemotherapies combined with targeted drugs in advanced colorectal cancer. Methods: Pubmed, Embase, CNKI, Wanfang database, and VIP database were used to search a variety of chemotherapy regimens and their co-targeted drug therapy in advanced colorectal cancer. A systematic review of comparing chemotherapy plus targeted therapy with chemotherapy alone was conducted by Meta-analysis software Review Manager 5.1.7. Results: Eleven trials and 973 patients in total were analyzed in this meta-analysis. The overall response rate (CR+PR) of the chemotherapy combined with targeted drugs was obviously higher than that of the chemotherapy alone (OR=0.48, 95% CI:0.37-0.63, P<0.001). No difference in the five adverse reactions (nausea, vomiting, diarrhea, liver damage, bone marrow suppression, and neurotoxicity) was found between the chemotherapy combined with targeted drugs and the chemotherapy alone (P>0.05). Conclusion: In the advanced colorectal cancer in Chinese patients, the efficacy of the chemotherapy combined with targeted drugs is more dominant than chemotherapy alone. The adverse reactions are not revealed any significant differences in the 2 therapy methods.