Objective To establish the association between genetic polymorphisms of HLA-DMA and HLA-DMB and risk of developing trichloroethylene-induced medicamentosa-like dermatitis (TIMLD). Methods Sixty-one cases were medically confirmed to have been affected with TIMLD and 60 controls were selected from exposed workers who were free from TIMLD.The TIMLD cases and controls were similar in terms of age, sex, and duration of exposure. DNA was extracted both from the TIMLD cases and controls, HLA-DMA and HLA-DMB loci were amplified by using Touchdown PCR, and the alleles and genotypes were confirmed by restriction fragment length polymorphism (RFLP) and direct sequencing. Finally, the frequencies of HLA-DMA and HLA-DMB variants were compared between the two groups. Results The results showed that the frequency of HLA-DMA*0101 and HLA-DMB*0103 alleles was significantly increased in TIMLD patients than in controls (71.3% vs. 55.0% for HLA-DMA*0101; P＜0.05) (11.5% vs. 3.3% for HLA-DMB*0103; P＜0.05). In addition, the frequency of HLA-DMA*0102-*0102 homozygous genotype was also significantly higher in the controls than in the patients (25.0% vs.8.2%, P＜0.05), whereas the frequency of heterozygous HLA-DMB *0101-*0102 genotype was lower in the patients in comparison with the controls. Conclusion The polymorphisms of HLA-DM may be associated with the susceptibility to TIMLD.