Objective To explore the association between death receptor (DR) 4 gene polymorphism and the predis-position of ulcerative colitis(UC). Methods DR4(rs20575)genotypes were determined by direct sequencing in a total of 147 UC patients and 244 healthy controls. Logistic regression analysis was employed to assess the relationship be-tween DR4 (rs20575)gene polymorphism and UC. Results Compared to the controls, the frequencies of variant allele(G)and genotype(CG+GG) of DR4(rs20575)were significantly increased in UC patients(5.78% vs 1.23%,P=0.001,OR=4.930,95%CI1.192-12.651;7.48% vs 2.46%,P=0.025,OR=3.208,95%CI1.161-8.869). According to the Tru-elove &Witt Activity Index, the severity of UC was further stratified into the mild, moderate and severe disease. In re-sult, variant allele (G)and genotype(CG+GG)in DR4(rs20575)were significantly higher in patients with moderate and severe UC than those with mild UC (10.64% vs 3.50%,P=0.020,OR=3.282,95%CI1.208-8.916; 14.89% vs 4.00%,P=0.028,OR=4.200,95%CI1.165-15.146). DR4(rs20575) mutant allele and genotype frequencies between extensive colitis and distal colitis were no statistical difference(P>0.05). Conclusion The genetic polymorphism of DR4(rs20575)is significantly related with the susceptibility to UC, as well as severity of the disease in this cohort of Chinese pa-tients.