Cyclooxygenase-2 (COX-2) is an inducible enzyme converting arachidonic acid to prostaglandins and playing important roles in cancer etiology. The -765G>C and 8473T>C polymorphisms have been implicated in cancer risk. However, the results on the association between the two COX-2 polymorphisms and cancer risk are conflicting. To derive a more precise estimation of the association between them, we performed a meta-analysis of 8,090 cancer cases and 11,010 controls concerning -765G>C polymorphism and 14,283 cancer cases and 15,489 controls concerning 8473T>C polymorphism from 33 case-control studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, individuals with the -765GC or GC/CC genotypes were associated with higher cancer risk than those with the -765GG genotype and in the stratified analysis this effect maintained in colorectal carcinoma or esophageal cancer of Asian descents. Overall, no significant cancer risk of 8473T>C polymorphism was found. Stratified by cancer types, the variant 8473CC was associated with a decreased risk in breast cancer, compared with the TT or TC/TT genotypes and in lung cancer subgroup after sensitive analysis, there was a decreased risk in CC versus TT, TC versus TT and the dominant models. Moreover, a decreased risk of lung cancer was observed among smokers in the dominant model. In summary, this meta-analysis suggesting that -765G>C may cause an increased risk of colorectal carcinoma and esophageal cancer in Asian descents while 8473T>C polymorphism may cause a decreased risk of breast and lung cancer.