Considering the important role of TNF-a, LT-a, TNFR1 and TNFR2 in the pathogenesis of severe sepsis, we hypothesized that genetic variation in TNF, LTA, TNFRSF1A and TNFRSF1B might be associated with susceptibility to and outcomes from severe sepsis in Chinese Han population. To test this hypothesis, we conducted a relatively large-scale case-control study enrolling 432 severe sepsis patients, 384 sepsis patients and 624 healthy individuals to investigate the association of genetic variants in TNF, LTA, TNFRSF1A and TNFRSF1B with severe sepsis susceptibility and prognosis in Chinese Han population. Furthermore, we investigated the association between the genotypes of the TNF gene SNP rs1800629 and TNF-a concentration in culture supernatants of LPS simulated PBMCs obtained from healthy donors and in serum from severe sepsis patients.