p73 G4C14-A4T14 polymorphism has been hypothesised to be associated with the risk of cancer development by many epidemiological studies, however, the available results were conflicting. To derive a more precise estimation of association between the p73 G4C14-A4T14 polymorphism and risk of cancer, we performed a meta-analysis based on 8017 cancer cases and 11610 controls from 25 publications with 27 individual case-control studies. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. Overall, We found that the variant AT/AT homozygote was associated with a significantly increased risk of all types of cancer (homozygote comparison: OR = 1.35, 95% CI = 1.11-1.65; recessive model comparison: OR = 1.32, 95% CI = 1.11-1.58). In the subgroup analyses by ethnicity/country, the results suggested that AT/AT genotype was significantly associated with risk of cancer development among Caucasians and Asians, especially for the Americans and Japanese. Moreover, when stratifying by types of cancer, significantly increased cancer risks were observed for colorectal cancer, 'head and neck cancers' and 'other cancers'. Interestingly, when stratifying by source of controls, a significantly elevated risk was found among hospital-based studies but not among population-based studies. Limiting the analysis to the studies within Hardy-Weinberg equilibrium, the results were persistent and robust. No publication bias was found in the present study. This meta-analysis suggests that the p73 -AT allele may be a low-penetrant risk factor for cancer development.