Objective To investigate the effect of celecoxib on the secretion of MH7A inflammatory factor in fibroblast-like synoviocytes in rheumatoid arthritis (RA) induced by tumor necrosis factor-α (TNF-α). Methods MH7A cells were treated with 0, 2. 5, 5, 10, 20 or 40 μmol / L celecoxib for 24 h before detecting cell viability by MTT assay to screen non-toxic concentration. Enzyme-linked immunosorbent assay, real-time fluorescent quantitative PCR, and Western blot were used to detect levels of interleukin ( IL)-6, IL-1β, microRNA (miR)-129-5p, and high mobility group box-1 protein (HMGB1) in the supernatant of TNF-α-induced MH7A cells treated with 2. 5, 5 and 10 μmol / L celecoxib. A double-luciferase reporter gene assay was used to detect the targeting relationship between miR-129-5p and HMGB1, and transfection of miR-129-5p mimics or HMGB1 siRNA into MH7A cells was performed to observe the effect of miR-129-5p overexpression or downregulation of HMGB1 expression on TNF-α-induced inflammatory factor secretion in MH7A cells. In addition, an miR-129-5p inhibitor was transfected into MH7A cells induced by TNF-α to observe the effect of low miR-129-5p expression on TNF-α-induced secretion of inflammatory factors in MH7A cells treated with 10 μmol / L celecoxib. Results Compared with 0 μmol / L, the activity of MH7A cells treated with 2. 5, 5 and 10 μmol / L celecoxib exhibited no significant difference (P> 0. 05). However, the activity of MH7A cells decreased significantly after 20 and 40 μmol / L celecoxib treatment (P<0. 05). Under induction by TNF-α, 2. 5, 5 and 10 μmol / L celecoxib inhibited IL-6 and IL-1β levels in the supernatant of MH7A cells, as well as expression of HMGB1 protein, and promoted the expression of miR-129-5p in a concentration-dependent manner. miR-129-5p can target and bind to HMGB1 to negatively regulate its expression. After overexpression of miR-129-5p or downregulation of HMGB1 expression, levels of IL-6 and IL-1β in the supernatant of MH7A cells induced by TNF-α were significantly decreased ( P< 0. 05). Low expression of miR-129-5p significantly reversed the inhibitory effects of 10 μmol / L celecoxib on TNF-α-induced IL-6 and IL-1β levels in the supernatant of MH7A cells. Conclusions Celecoxib can inhibit TNF-α-induced inflammatory factor secretion by MH7A cells, and its mechanism may be related to the regulation of miR-129-5p / HMGB1.