p21 is a cyclin-dependent kinase inhibitor, which can arrest cell proliferation and serve as a tumor suppressor.Though many studies were published to assess the relationship between p21 rs1059234 polymorphism andvarious cancer risks, there was no definite conclusion on this association. To derive a more precise quantitativeassessment of the relationship, a large scale meta-analysis of 5,963 cases and 8,405 controls from 16 eligiblepublished case–control studies was performed. Our analysis suggested that rs1059234 was not associated withthe integral cancer risk for both dominant model [(T/T+C/T) vs C/C, OR=1.00, 95% CI: 0.84-1.18] and recessivemodel [T/T vs (C/C+C/T), OR=1.03, 95% CI: 0.93-1.15)]. However, further stratified analysis showed rs1059234was greatly associated with the risk of squamous cell carcinoma of head and neck (SCCHN). Thus, larger scaleprimary studies are still required to further evaluate the interaction of p21 rs1059234 polymorphism and cancerrisk in specific cancer subtypes.