ObjectiveTo investigate the effect of capecitabine versus 5-fluorouracil in advanced gastric cancer patients.MethodsWe searched PubMed, Cochrane Library, Embase, and other databases from database establishment to June 2022, containing randomized controlled trials (RCT) on capecitabine and 5-fluorouracil in advanced gastric cancer patients. A meta-analysis was conducted to evaluate the effect of capecitabine versus 5-fluorouracil on overall response rate, neutropenia, thrombocytopenia, stomatitis, hand-foot syndrome, nausea and vomiting, alopecia, and diarrhea.ResultsEight RCTs with a total of 1998 patients with advanced gastric cancer were finally included, including 982 with capecitabine and 1016 with 5-fluorouracil. Compared with 5-fluorouracil, capecitabine use was significantly associated with an improved overall response rate in patients (RR 1.13, 95% CI 1.02–1.25,P=0.02). Compared with 5-fluorouracil, treatment with capecitabine was significantly associated with decreased neutropenia events (RR 0.78, 95% CI 0.62–0.99,I2= 86%,P=0.04), and a decreased risk of stomatitis (RR 0.73, 95% CI 0.64–0.84,I2= 40%,P< 0.0001) in patients with advanced gastric cancer. In terms of hand-foot syndrome, capecitabine was associated with increased hand-foot syndrome events than 5-fluorouracil (RR 2.00, 95% CI 1.21–3.31,P=0.007). In terms of thrombocytopenia, nausea and vomiting, alopecia, and diarrhea, the effect of capecitabine and 5-fluorouracil were similar (P> 0.05).ConclusionsCompared with 5-fluorouracil, capecitabine treatment improves the overall response rate and reduces the risk of neutropenia and stomatitis in advanced gastric cancer patients. It should be noted that capecitabine treatment may also increase the occurrence of hand-foot syndrome. Capecitabine is similar to 5-fluorouracil in causing thrombocytopenia, nausea and vomiting, alopecia, and diarrhea.