Aims: To investigate the association between four single nucleotide polymorphisms (SNP) of peroxisome proliferator-activated receptor-gamma (PPAR gamma), and additional gene-gene interaction with essential hypertension (EH) in Chinese Han population. Methods: A total of 1280 subjects (625 males, 655 females), with a mean age of 51.2 +/- 15.1 years old, including 628 EH patients and 652 normal subjects were included in the study, including the genotyping of polymorphisms. Logistic regression model was used to examine the association between 4 SNP and EH, odds ratio (OR) and 95% confident interval (95% CI) were calculated. Generalized MDR (GMDR) was employed to analysis the interaction among four SNPs. Results: EH risk was significantly higher in carriers of Ala allele of the rs1805192 polymorphism than those with Pro/Pro (Pro/Ala + Ala/Ala versus Pro/Pro, adjusted OR (95% CI) = 1.54 (1.20-1.89). In addition, we also found a significant association between rs4684847 and EH, EH risk was significantly higher in carriers of T allele of the rs4684847 polymorphism than those with CC (CT + TT versus CC, adjusted OR (95% CI) = 1.32 (1.16-2.43). There was a significant two-locus model (P = 0.0107) involving rs1805192 and rs4684847, indicating a potential gene-gene interaction between rs1805192 and rs4684847. Subjects with Pro/ Ala or Ala/Ala and CT or TT genotype have highest EH risk, compared to subjects with Pro/Pro-CC genotype, OR (95% CI) was 3.26 (1.90-5.80), after covariates adjustment. Conclusions: Our results support an important association between rs1805192 and rs4684847 minor allele of PPAR gamma and EH, and additional interaction between rs1805192 and rs4684847.