Objective: To observe the clinical effect of arthrocentesis combined with liquid phase concentrated growth factor (CGF) injection in the treatment of unilateral temporomandibular joint osteoarthritis (TMJOA), in order to provide a new treatment option for TMJOA patients. Methods: In this non-randomized controlled study, patients diagnosed with unilateral TMJOA who visited the center for temporomandibular joint disorder and orofacial pain of Peking University School and Hospital of Stomatology from June 2021 to January 2023 were selected as research objects. The patients were divided into experimental group and control group, which were selected by patients themselves. The experimental group received arthrocentesis combined with liquid phase CGF injection and the control group received arthrocentesis combined with HA injection. Both groups were treated 3 times, once every two weeks. The clinical effect was evaluated by the maximum mouth opening, pain value and the degree of mandibular function limitation 6 months after treatment. The change of condylar bone was evaluated by cone beam CT (CBCT) image fusion technology before and after treatment. Results: A total of 20 patients were included in the experimental group, including 3 males and 17 females, with an average age of (34.40±8.41) years. A total of 15 patients were included in the control group, including 1 male and 14 females, with an average age of (32.20±12.00) years. There was no statistical difference in general information between the two groups (P > 0.05). There were no statistical differences in the mouth opening, pain value and the degree of jaw function limitation between the two groups before treatment (P > 0.05), and all of them improved 6 months after treatment compared with before treatment (P < 0.05). However, the mouth opening of experimental group was significantly higher than that of control group 6 months after treatment (P < 0.05), and the degree of jaw function limitation was significantly lower than that of control group (P < 0.05). CBCT 2D images showed that the condylar bone of both groups was smoother after treatment than before treatment, and image fusion results showed that 10 patients (50.0%) in the experimental group and 5 patients (33.3%) in the control group had reparative remodeling area of condylar bone, and there was no statistical difference between them (P > 0.05). Except for one CGF patient, the other patients in both groups had some absorption areas of condylar bone. Conclusion: The arthrocentesis combined with liquid phase CGF injection can improve the clinical symptoms and signs of unilateral TMJOA patients in short term, and is better than HA in increasing mouth opening and improving jaw function. CBCT fusion images of both patient groups show some cases of condylar bone reparative remodeling and its relevance to treatment plans still requires further study.