Objective. To systematically evaluate the clinical efficacy and safety of karelizumab combined with apatinib in the treatment of advanced gastric cancer. Methods. The published databases were searched by computer, Chinese: China Biomedical Literature Database (CBM), Wanfang Journal Database, China national knowledge infrastructure (CNKI), and China Science and Technology Journal Database (VIP); English: Embase, Cochrane library, and PubMed. The search time is from the establishment of the database to May 2022, and clinical randomized controlled trials (RCT) with advanced gastric cancer as the research object and karelizumab combined with apatinib as the research variables are collected. According to the bias risk evaluation standard of Cochrane System Evaluator’s Manual, the literatures meeting the inclusion standard were evaluated for bias risk, and the meta-analysis was conducted by Review Manager 5.3. Results. A total of 20 articles with 1150 patients were included in this study. All the included 20 articles reported objective remission rate (ORR), and the heterogeneity among 20 studies was low ( P > 0.05 , I 2 = 0 %). The ORR of gastric cancer patients in the observation group was significantly higher than that in the blank group [odds ratio OR = 1.97 , 95% CI [1.53, 2.62], P < 0.01 ). All the included 20 articles reported disease control rate (DCR), and the heterogeneity among 20 studies was low ( P = 0.87 , I 2 = 0 %). The ORR of gastric cancer patients in the observation group was significantly higher than that in the blank group ( OR = 3.09 , 95% CI [2.29, 4.16], P < 0.01 ). Three articles in the included literature reported the median OS, and the heterogeneity among the three studies was low ( P = 0.70 , I 2 = 0 %). The median OS of gastric cancer patients in the observation group was significantly higher than that in the blank group ( MD = 3.97 , 95% CI [3.61, 4.39], P < 0.01 ). There are three reports on median progression-free survival (PFS) in the included literature, and there is high homogeneity among the three studies ( P < 0.00001 , I 2 = 86 %). There is no statistical difference between the median PFS of gastric cancer patients in the observation group and the blank group ( MD = 1.21 , 95% CI [−1.20, 3.70], P = 0.29 ). The incidence of hypertension in the observation group was significantly higher than that in the blank group [ OR = 6.19 , 95% CI (1.91, 20.20), P = 0.003 ]. The incidence of proteinuria in the observation group was significantly higher than that in the blank group [ OR = 3.97 , 95% CI (1.08, 14.59), P = 0.03 ]. There was no significant difference in the incidence of other adverse reactions such as hand-foot syndrome, diarrhea, and myelosuppression between the observation group and the blank group. The levels of IFN-γ and TNF-α in the observation group were significantly higher than those in the blank group ( P < 0.0001 ). The levels of IL-10, IL-4, and tumor markers in the observation group were significantly lower than those in the blank group ( P < 0.05 ). Egger’s test showed that there was no publication bias in the 20 included studies ( P > 0.05 ). Conclusion. Karelizumab combined with apatinib is effective in the treatment of advanced gastric cancer, with low incidence of adverse reactions and high safety. However, a large number of multicenter, large sample size, and high-level RCT are needed for clinical verification.