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Rab22a is a member of the Ras-related small GTPase family, which plays a key role in regulating the recycling of cargo proteins entering cells through clathrin-independent endocytosis (CIE). Rab22a is overexpressed in different cancer types, including liver cancer, malignant melanoma, ovarian cancer and osteosarcoma. However, its oncogenic role remains unknown. In this study, we found that silencing of Rab22a suppressed the migration and invasion of lung cancer cells. Furthermore, Rab22a interacts with CD147, and knockdown of Rab22a blocks CD147 recycling and promotes CD147 degradation. Taken together, our findings indicate that Rab22a enhances recycling of CD147, which is required for lung cancer cell migration and invasion,and targeting CD147 recycling may be a rational strategy for lung cancer therapy.Knockdown of Rab22a inhibits lung cancer cell migration and invasion.Rab22a cooperates with CD147 to mediate lung cancer cell migration and invasion.Rab22a interacts with CD147 and affects the recycling of CD147.Knockdown of Rab22a promotes CD147 ubiquitin-proteasome degradation in a time-dependent manner.