Objective：This study aims to explore the role of ubiquitin-editing enzyme A20 in inhibiting alveolar bone resorption in mice with experimental periodontitis and the potential mechanism underlying it. Methods：Twenty mice were randomly divided into 4 groups：normal group with no periodontitis（control），periodontitis and PBS treatment（PBS+P） group，periodontitis and negative control adeno-associated virus（AAV） treatment（AAV+P） group，periodontitis and AAV targeting A20（AAV-A20） treatment（A20+P） group. Silk ligation combined with local application of Porphyromonas gingivalis（P. gingivalis） suspensions was used to construct the experimental periodontitis model. Gingiva of mice were locally injected with AAV-A20 to achieve A20 overexpression in the periodontal tissue. Immunofluorescence for A20 was used to verify AAV-A20 transfection efficiency in the periodontal tissue. microcomputed tomography（Micro-CT），haematoxylin and eosin（HE） staining and tartrate-resistant acid phosphatase（TRAP） staining were employed to compare the degree of alveolar bone resorption and the number of osteoclasts between the maxillary first and second molar of mice. Expressions of RANKL（receptor activator of nuclear factor-κВ ligand） and autophagy-related molecules in the periodontal tissue of mice were detected by immunohistochemical staining. Results：Compared with the PBS+P and AAV+P group，mice in the A20+P group exhibited decreased autophagic level and RANKL expression in their peridontal tissues. Besides，the number of TRAP positive osteoclasts between the maxillary first and second molar and alveolar bone resorption in mice were also repressed in the A20+P group. Conclusion：A20 alleviates alveolar bone resorption in mice with experimental periodontitis through negative regulation of autophagy，and A20 is expected to be a new target for periodontitis treatment.