Knockdown of USP35 combined with oncolytic virus significantly promotes the immune infiltration of CD8+ T cells and the release of IFNβ and inflammatory factors CXCL10 and CCL5, ultimately inhibiting the growth of malignant melanoma, Overall, our findings identify USP35 as a previously undescribed regulator of MAVS pathway, and targeting USP35 provides a strategy for immunotherapy of malignant melanoma. The gene discussed is MAVS; the disease is melanoma.