OBJECTIVE To find out whether tumor necrosis factor (TNF)-alpha-308 and TNF-alpha-238 locus (G-->A) mutation within the TNF-alpha gene promoter region is associated with susceptibility to occupational stress. METHODS 169 pipelining workers were investigated using the occupational stress measuring instrument. The subjects were divided into high and low strain groups according to the job strain score of the questionnaire. By means of polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) techniques, TNF-alpha gene polymorphisms of all subjects were analyzed. RESULTS There were 34 workers with genotype -308G/G and 4 with -308G/A genotype in the low strain group while in the high strain group, there were 117 workers with genotype -308G/G and 10 with -308G/A genotype and 1 with -308A/A. No significant difference in -308 genotype was found between the two groups (chi2 = 0.0001, P > 0.05). There were 30 workers with genotype -238G/G and 7 with -238G/A genotype and 1 with -238A/A in the low strain group while there were 118 workers with genotype -238G/G and 10 with -238G/A genotype in high strain group. The frequencies of TNF-alpha-238A in the low strain groups were significantly higher than that in high strain groups (chi2 = 5.45, P < 0.05). CONCLUSIONS TNF-alpha promoter G238A polymorphism is associated with occupational stress. There is no evident relationship between TNF-alpha promoter G308A polymorphism and susceptibility to occupational stress.