Objective: To investigate the expression level and clinical significance of ATP6V1A, a subunit of vacuolar-type proton pump (V-ATPase), in colonic mucosal tissues of patients with ulcerative colitis (UC). Methods: A total of 116 UC patients were enrolled. According to the modified Mayo score, they were divided into the remission group (n=35) and the active group (n=81). The patients in the active stage of UC were further stratified into the mild subgroup (n=31), moderate subgroup (n=27) and severe subgroup (n=23) based on the modified Truelove and Witts classification criteria. Meanwhile, 50 healthy subjects who underwent colonoscopy in our hospital during the same period were selected as the control group. For UC patients, colonic mucosal tissue samples were collected from the most prominent lesion area under colonoscopy, for the control group, samples were obtained from the colonic mucosa with normal endoscopic morphology at 20 cm from the anus. Immunohistochemistry was employed to detect the expression of ATP6V1A in colonic mucosal tissues. The correlation between ATP6V1A expression and modified Mayo score of UC patients was analyzed, and the value of ATP6V1A expression in evaluating the occurrence of severe condition in active UC patients was assessed. Results: Compared with the control group, the expression level of ATP6V1A in the remission group and active group decreased (P<0.05), and the expression in the active group was lower than that in the remission group (P<0.05). Among patients with active UC, the expression level of ATP6V1A declined gradually with the aggravation of disease severity (P<0.05). Moreover, ATP6V1A expression in colonic mucosal tissues of UC patients was negatively correlated with the modified Mayo score (P<0.05). Logistic regression analysis revealed that low ATP6V1A expression (OR=0.451) and high modified Mayo score (OR=2.787) were independent risk factors for severe condition in patients with active UC (P<0.05). Receiver operating characteristic (ROC) curve analysis demonstrated that the area under the curve (AUC) of ATP6V1A expression level for evaluating severe condition in active UC patients was 0.758. Conclusion: ATP6V1A is lowly expressed in the colonic mucosal tissues of UC patients, and its expression level is correlated with disease severity, which has important value in evaluating the occurrence of severe condition in patients with active UC.