Axin2 is involved in the regulation of Wnt/β-catenin pathway and implicated in cancer development and progression. The association between AXIN2 rs2240308 polymorphism and cancer risk has been examined in several case-control studies, but the conclusions were conflicting. Here we performed a meta-analysis to evaluate the role of rs2240308 in cancer risk. A total of 8 studies were included in this meta-analysis (1559 cancer cases and 1503 controls). The pooled odds ratios (OR) and the 95% confidence intervals (CIs) were assessed to evaluate the association of the AXIN2 rs2240308 polymorphism with a susceptibility to cancer. A significantly decreased overall cancer risk was observed in the homozygous (TT vs. CC), heterozygous (CT vs. CC), dominant (CT+TT vs. CC) and allelic (T vs. C) models (P < 0.005), rather than that in the recessive (TT vs. CT+CC) model (P = 0.092). AXIN2 polymorphism rs2240308 was also associated with decreased cancer risk under all five models in lung cancer. However, AXIN2 rs2240308 polymorphism was not associated with cancer risk under any above model in Turkish population and under homozygous, heterozygous, recessive models in Japanese population. These findings indicate that AXIN2 rs2240308 polymorphism significantly and race-specifically correlates with decreased cancer risk.