Many studies have reported the association between the FASLG -844T/C polymorphism and cancer risk, but the data are remaining controversial. A pooled analysis was performed to assess this relationship comprehensively. Medline, PubMed, Embase and Web of Science were searched, and data were extracted and cross-checked independently by three authors. A total of 18 published studies including 22389 subjects were involved in this analysis. Overall, the -844C allele was associated with a significantly increased cancer risk (for CC versus TT: OR=1.23, 95% confidence interval (CI)=1.04-1.45; for CC+TC versus TT: OR=1.15, 95% CI=1.01-1.30; for CC versus TT+TC: OR=1.20, 95% CI=1.05-1.38). In the subgroup analysis by ethnicity, significantly elevated risks were found among Asians (for CC versus TT: OR=1.61, 95% CI=1.37-1.89; for CC+TC versus TT: OR=1.36, 95% CI=1.16-1.60; for CC versus TT+TC: OR=1.44, 95% CI=1.22-1.70). In the subgroup analysis by study design, significantly increased risks were found among population-based case-control studies (for CC versus TT: OR=1.40, 95% CI=1.06-1.84; for CC+TC versus TT: OR=1.25, 95% CI=1.01-1.55; for CC versus TT+TC: OR=1.31, 95% CI=1.06-1.61). These findings indicate that the FASLG -844C allele is emerging as a low-penetrant cancer susceptibility allele for cancer development. However, more comprehensive understanding of the association would certainly have an immense prospect in the promising field of individualised preventive care.