AIM: To investigate the molecular mechanism of lncRNA HOTAIR regulating miR-206 on the proliferation and apoptosis of rheumatoid arthritis synovial cells. METHODS: The synovial tissue from 30 cases of rheumatoid arthritis were collected. Rheumatoid arthritis synovial cells MH7A were cultured. The experiment was divided into si-NC group, si-HOTAIR group, miR-NC group, miR-206 mimic group, si-HOTAIR+NC inhibitor group, si-HOTAIR+miR-206 inhibitor group. Real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the expression levels of HOTAIR and miR-206 in cells. CCK-8 method to detect cell proliferation; flow cytometry to detect cell apoptosis; Western blot to detect cell protein expression of CyclinD1, p21, Bax and Bcl-2; dual luciferase reporter assay to detect HOTAIR and miR-206 targets To combination relationship. RESULTS: Compared with the healthy control group, the expression level of HOTAIR in patients with rheumatoid arthritis was significantly up-regulated, and the expression level of miR-206 was significantly down-regulated (P<0.05). Compared with the si-NC group, the HOTAIR expression level in the si-HOTAIR group was significantly down-regulated, the cell survival rate were significantly down-regulated, and the apoptosis rate were significantly up-regulated (P<0.05). Compared with the miR-NC group, the expression level of miR-206 in the miR-206 mimic group was significantly up-regulated, the cell survival rate were significantly down-regulated, and the apoptosis rate were significantly up-regulated (P<0.05). Compared with the si-HOTAIR+NC inhibitor group, the cell survival rate in the si-HOTAIR+miR-206 inhibitor group were significantly up-regulated, and the apoptosis rate were significantly decrease (P<0.05). CONCLUSION: Inhibiting the expression of HOTAIR and up-regulating the expression of miR-206 can reduce the proliferation of rheumatoid arthritis synovial cells and promote apoptosis.