The main aim of the present study was to measure hypoxia-inducible factor-1α (HIF-1α) in serum and colonic mucosa of ulcerative colitis (UC) patients and to analyze its role in the pathogenesis, disease activity and severity of UC. A total of 47 UC patients and 13 UC in remission patients were recruited for the present study. Ten healthy subjects were also included to serve as controls. HIF-1α in the serum was measured using ELISA. The citrate-microwave-SP immunohistochemical method was used to measure the expression of HIF-1α in colonic mucosa. The results showed that, HIF-1α in serum was notably higher in UC patients (73.21±28.65) than UC in remission patients (44.54±14.75) and controls (42.83±15.49). The difference between UC patients and UC in remission patients was significant (P<0.05). A correlation analysis revealed that, the HIF-1α level in serum was positively associated with disease activity, disease severity and endoscopic grade. The expression of HIF-1α in colonic mucosa of UC patients was (58.05±13.83) higher than that in UC in remission patients (3.00±2.72) and controls (3.04±2.69) and this difference was statistically significant (P<0.05). A positive correlation was identified between the expression of HIF-1α in colonic mucosa and the disease activity, severity and endoscopic grade. Thus, the present findings indicated that, HIF-1α is likely to play an important role in the pathogenesis of UC and may serve as a biomarker to evaluate disease activity and severity in UC patients.