Objective:To systematically review the correlation between serum Mac-2-binding protein glycosylation isomer (M2BPGi) level and hepatocellular carcinoma (HCC).Methods:The PubMed, Embase, Ovid, CBM (China Biology Medicine), Wanfang Databases were searched for studies on the correlation between serum M2BPGi level and HCC. After the selection process, 16 papers were included in this systematic review. A total of 7 810 patients were enrolled in the study, including 629 patients with HCC. The RevMan 5.2 software and R 4.1.2 software were used for the meta-analysis.Results:The elevated level of M2BPGi was significant positively associated with the risk of HCC( HR=2.28, 95% CI: 1.82-2.86, P<0.01). In Japan and Chinese groups, the elevated level of M2BPGi was significantly associated with an increased risk of HCC, with HR of 4.77 (95% CI: 2.73-8.32, P<0.01) and 2.04 (95% CI: 1.38-3.03, P<0.01), respectively. The elevated level of M2BPGi in three subgroups of people with untreated hepatitis C virus (HCV) infection, during treatment of hepatitis B virus (HBV) infection, and after HCV virological cure predicted an increased risk of HCC, with HR of 3.14 (95% CI: 2.19-4.50, P<0.01), 2.09 (95% CI: 1.36-3.22, P<0.01) and 5.07 (95% CI: 1.57-16.42, P<0.01), respectively. Conclusion:The elevated level of M2BPGi can indicate the increased risk of HCC, which can be used as one of the early warning indicators of HCC.