PTEN (phosphatase and tensin homologue), as a tumor suppressor gene, plays a significant role in regulatingcell growth, proliferation, and apoptosis. Results from published studies for association between the PTEN IVS4I/D (rs3830675) polymorphism and cancer risk are inconsistent and inconclusive. We therefore conducted ameta-analysis to evaluate the potential association between PTEN IVS4 I/D polymorphism and risk of cancerin detail. We searched PubMed (Medline) and EMBASE web databases to cover all relevant studies publisheduntil December 2013. The meta-analysis was carried out and pooled odds ratios (ORs) and 95% confidenceintervals (95%CIs) were used to appraise the strength of association. A total of 1,993 confirmed cancer casesand 3,200 controls were included from six eligible case-control studies. Results from overall pooled analysissuggested a significant effect of the PTEN IVS4 I/D polymorphism and cancer risk in all genetic models, i.e.,allele (I vs D: OR=0.743, 95%CI=0.648 to 0.852, p=0.001), homozygous (II vs DD: OR=0.673, 95%CI=0.555 to0.816, p=0.001), heterozygous (ID vs DD: OR=0.641, 95%CI=0.489 to 0.840, p=0.001), dominant (II+ID vs DD:OR=0.626, 95%CI=0.489 to 0.802, p=0.001) and recessive (II vs DD+ID: OR=0.749, 95%CI=0.631 to 0.889,p=0.001). Significant publication bias was detected during the analysis. The present meta-analysis suggests thatthe PTEN IVS4 I/D polymorphism is significantly associated with reduced risk of cancer. However, future largerstudies with other groups of populations are warranted to clarify this association.