Objective To investigate the correlation of gene polymorphisms of TNF-α and its receptor with rheumatoid arthritis (RA) susceptibility and the related serological markers in the Han nationality living in northwest China. MethodsThe gene polymorphisms of TNF-α and its receptor (TNFA -857C>T, TNFA -863C>A,TNFA -308G>A,TNFA -238G>A,TNFR1-383A>C,TNFR2-exonT>G) were determined by high resolution melting (HRM) in 452 RA patients and 356 controls in a case-control manner. Anti-cyclic citrullinated protein antibodies (anti-CCP) and rheumatoid factors (RF) were measured by clinical conventional methods, and their association with the gene polymorphisms of TNF-α and its receptor was analyzed. ResultsSignificant differences were found in the distribution frequencies of TNFA -308GA and -863CA between RA cases and healthy controls (P=0.001,P=0.002), but not in the frequencies of TNFA -238GA,TNFA -238AA,TNFR2-exonTG or TNFR2-exonGG (P=0.701,P=0.999,P=0.825, P=0.330). In addition, significant differences were also found in the distribution frequencies of TNFA haplotypes of -238G/-308A/-863C(GAC), -238G/-308G/-863A(GGA) and -238G/-308G/-863C(GGC) between the two groups (P=0.016, P=0.033, P=0.023). Furthermore, we found that RA serological markers (RF, anti-CCP) were not significantly correlated with the gene polymorphisms of TNF-α and its receptors. ConclusionTNFA -308GA and TNFA -863CA are associated with RA susceptibility in Han nationality living in northwest China, so are the TNFA haplotypes of GAC, GGA and GGC. Gene polymorphisms TNF-α and its receptor have no significant correlation with RA serological markers.