Abstract: Objective:To investigate the relationship of –308 bp polymorphism in tumor necrosis factor-α (TNF α) gene and + 252 bp in lymphotoxin-α (LT α) gene wi th the cl inical course and outcome of non-Hodgkin's lymphoma (NHL). Methods:The single base change in TNF α gene and LT α gene was analyzed among 96 Chinese patients with NHL and 72normal controls by using PCR-restrictive fragment length polymorphism (RFLP). The clinical data were collected and survival analysis was performed. Results: In NHL patients, no sta-tistically significant association was found between the presence of a given TNF/LT haplotype status and clini -cal variables such as age, sex, disease stage, and so on. The patients carrying low-risk haplotype achieved a more sensitive response to first-line therapy than that in patients with high-risk haplotype (70.4% v 45.2%;P=0.018 ). The estimated 1-year progression-free survival rates in the high-risk and low-risk groups were 66.67% and 87.5% , respectively (log-rank test, P=0.0231). Kaplan-Meier method showed that the estimated 2-year and 4-year overall survival rates were 39.95% and8.32% in patients carrying high-risk haplotypes and 65.13% and 46.52% in patients carrying low-risk haplotypes, respectively (log-rank test,P=0.0012). In multi-variate Cox regression models, the TNF/LT haplotype status was found to be a risk factor for outcome of NHL (P=0.034 ). Conclusion:There is an association between TNF/LT haplotype status and response to therapy and outcomes of NHL in Canton area, China. Detecting TNF/LT haplotype may be a sensitive method to evalu- ate the outcome of NHL.