The genetic factors predisposing to ulcerative colitis (UC) have remained totally unclear to date. This study aimed to investigate the role of HLA-DRB1 genetic polymorphism in the susceptibility to develop UC in Chinese patients. HLA-DRB1 genotyping was carried out in 72 unrelated patients with UC and 314 healthy controls by using polymerase chain reaction-sequence-specific primers (PCR-SSP). All of the patients and healthy controls are Han people in China. The frequency of DRB1*07 allele was increased in UC patients compared with healthy controls (19.4% vs. 9.2%, P = 0.0229, OR = 2.372, 95%CI: 1.181-4.766), but the significance disappeared when given Bonferroni correction (P(C) = 0.2977). Furthermore, compared with healthy controls, although HLA-DRB1*07, DRB1*16/DRB1*09 and DRB1*07/DRB1*12 genotypes were increased in frequency in the patients with extensive colitis, and the patients without extraintestinal manifestations (EIMs) carried an increased frequency of HLA-DRB1*07 and DRB1*07/DRB1*12 genotypes, these differences did not reach statistical significance after Bonferroni correction. HLA-DRB1 alleles showed no strong association with UC, and no HLA-DRB1 alleles or genotypes were strongly associated with clinical subgroups of UC in Chinese patients.