Published data on any association between the CYP2E1 RsaI/PstI (c1/c2) polymorphism and liver cancer risk among east Asians are inconclusive. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to derive a more precise estimation of the relationship. A literature search of Pubmed, Embase, Web of science and CBM databases from inception through July 2012 was conducted. Twelve case-control studies were included with a total of 1,552 liver cancer cases and 1,763 healthy controls. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association under five genetic models. When all the eligible studies were pooled into the meta-analysis, the results showed that the c2 allele and the c2 carrier (c2/c2 + c2/c1) of RsaI/PstI polymorphism were associated with decreased risk of liver cancer among east Asians (c2 vs. c1: OR = 0.75, 95%CI: 0.59-0.95, P = 0.016; c2/c2 + c2/c1 vs. c1/c1: OR = 0.76, 95%CI: 0.58-1.00, P = 0.050). In the stratified analysis by country, significant associations were observed between RsaI/PstI polymorphism and decreased risk of liver cancer among the Chinese population (c2 vs. c1: OR = 0.70, 95%CI: 0.54-0.91, P = 0.007; c2/c2 + c2/c1 vs. c1/c1: OR = 0.72, 95%CI: 0.54-0.95, P = 0.020), but not among Japanese and Korean populations. Results from the current meta-analysis indicates that the c2 allele of CYP2E1 RsaI/PstI (c1/c2) polymorphism may be a protective factor for HCC among east Asians, especially among China populations.