Objectives To systematically review the association between TM6SF2 (transmembrane six superfamily member 2- rs58592426) polymorphism and liver lesion and the severity of liver fibrosis. Methods We electronically searched databases including PubMed, CNKI, WanFang Data and CBM from inception to January 27, 2016, to collect cross-sectional studies about the association between the TM6SF2 polymorphism and the liver lesion and the severity of liver fibrosis. Two reviewers independently screened literature, extracted data and assessed the methodological quality included studies. Then, meta-analysis was performed using Stata 12.0 software. Results A total of 23 studies including 96 594 patients were included. The results of meta-analysis showed that: TM6SF2 polymorphism was associated with increased risk of the severity of liver fibrosis, the levels of TG, TC and LDL-C (all P values < 0.05). Carriers of the T allele showed lower levels of TG, TC, and LDL-C. Carriers of the T allele revealed higher levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) when compared with homozygous EE. Conclusion TM6SF2 polymorphism is associated with lipid traits in different population, the variants shows lower levels of lipid traits in blood serum and increases the risk of the severity of liver fibrosis and liver lesion.