The tumor suppressor gene P53 plays an important role in carcinogenesis, and the P53 pathway is central both in reducing cancer frequency and in mediating the response of cancer therapies. MDM2, MDM4 and Hausp genes are all critical regulators of the tumor suppressor P53. Many studies have evaluated the association of single nucleotide polymorphisms (SNPs) in P53 pathway with the risk of common cancers. However, the results are still inconclusive. In this work, we analyzed the association of SNPs in P53 (rs1042522), MDM2 (rs2279744), MDM4 (rs1380576) and Hausp (rs1529916) genes with gastric cancer in a hospital-based Chinese Han population (642 cases and 720 cancer-free controls). We found that the polymorphisms of P53 (rs1042522) and MDM2 (rs2279744) are associated with gastric cancer risk, whereas no significant association was observed between variant genotype of other two polymorphisms (MDM4 rs1380576 and Hausp rs1529916) and gastric cancer risk.