BACKGROUND The aim of this study was to investigate the clinical significance of NLRP3 and HMGB1 in patients with active ulcerative colitis. MATERIAL AND METHODS This was a prospective observational study which included a total of 62 cases with active ulcerative colitis during January 2017 to December 2018. The patients were divided into a mild/moderate group or a severe group according to Sutherland Disease Activity Index (DAI) score. Clinical activity index and endoscopic index were used to determine the severity of UC. Serum levels of NLRP3, HMGB1, endothelin-1, IL-1ß, and TNF-alpha were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS Sutherland DAI score, clinical activity index, and endoscopic index were all significantly higher in severe patients than in the mild/moderate group. NLRP3, HMGB1, endothelin-1, IL-1ß, and TNF-alpha were significantly higher in severe UC patients. NLRP3 level was positively correlated with HMGB1, ET-1, IL-1ß, and TNF-alpha levels. Both NLRP3 and HMGB1 were positively correlated with Sutherland DAI score, clinical activity index, and endoscopic index. CONCLUSIONS Both serum NLRP3 and HMGB1 were elevated in UC patients, and the serum levels of NLRP3 were positively correlated with serum levels of HMGB1, ET-1, IL-1ß, and TNF-alpha, as well as severity of UC patients.