ObjectiveThe association between blood lipid levels and the risk of gastric cancer (GC) is well known. Therefore, to clarify this association, all relevant prospective cohort studies were included in this meta-analysis.MethodsOur study was registered in PROSPERO (CRD42022354899) prior to its commencement. A systematic review and meta-analysis were conducted in accordance with the PRISMA recommendations. Chinese databases (CNKI, CBM, Wanfang, and VIP) and English databases (PubMed, Embase, Web of Science, and the Cochrane Library) were systematically searched up to October 2022. This study included all relevant cohort studies that reported hazard ratios (HRs) or relative risks (RRs) and their corresponding 95% confidence intervals (95% CIs) to examine the association between various lipid profiles (e.g., total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) and the risk of developing gastric cancer (GC). Fixed effects or random effects models were used based on the level of heterogeneity among the studies, and these models were employed to obtain pooled hazard ratios. Additionally, sensitivity analysis and publication bias analysis were conducted to ensure the robustness and reliability of the findings.ResultsAfter conducting a systematic search, a total of 10 studies were selected out of 10,525 papers involving a total of 5,564,520 individuals. Among these individuals, there were 41,408 GC cases. The analysis revealed that the highest versus lowest serum total cholesterol (TC) concentration was associated with a pooled hazard ratio of 0.89 (95% CI = 0.87–0.92, I2= 15%). For triglycerides (TGs), the hazard ratio was 1.00 (95% CI = 0.96–1.04, I2= 37%), while for high-density lipoprotein cholesterol (HDL-C), the hazard ratio was 0.90 (95% CI = 0.86–0.93, I2= 0%). The hazard ratio for low-density lipoprotein cholesterol (LDL-C) was 0.96 (95% CI = 0.91–1.00, I2= 0%).ConclusionsBased on the results of this meta-analysis, it was found that serum TC and HDL-C levels were inversely correlated with the risk of GC. No association was observed between serum TG levels and the risk of GC. Similarly, no association was found between serum LDL-C levels and the risk of GC.