Hepatocellular carcinoma (HCC) is a heterogeneous disease with substantial genetic constitution. Previous work has evaluated the effect of prostaglandin-endoperoxide synthase 2 (PTGS2) variants (-765G/C, -1195A/G, and +8473T/C) on the development of HCC, but the conclusions are inconsistent. We conducted a meta-analysis in this work. Data from 7 case-control studies were combined to assess the association between PTGS2 variants and HCC. The risk of HCC (OR and 95% CI) was estimated using either the fixed- or the random-effects model according to the Q test. No significant association was identified for -765G/C and +8473T/C. However, we identified a significantly decreased risk in relation to the GG genotype of -1195A/G (OR = 0.70, 95% CI = 0.50-0.98 for GG versus AA). We also observed a similar decrease (OR = 0.47, 95% CI = 0.23-0.95 for GG versus AA) in Caucasian samples. Variant -1195A/G in the promoter PTGS2 may protect against the malignant progression of HCC. This significant association suggests that -1195A/G could be used as a biomarker of HCC.