Malignant melanoma has a poor prognosis because of its strong ability to invade tissues and metastasize. Immune checkpoint blockades significantly improve the clinical response in the development of melanoma. However, there are some obstacles to overcome, such as cost and limited application. Therefore, prospective approaches remain to be exploited. We designed cellular nanovesicles (NVs) expressing PD-1 to reactivate T cells by disrupting the PD-1/PD-L1 immunoinhibitory pathway. Furthermore, siNF90 was wrapped into PD-1 NVs to inhibit the proliferation of tumor cells. Such a dual target effect is helpful for the treatment of melanoma. In addition, our results showed that treatment with PD-1 @siNF90 NVs inhibited the growth of melanoma tumors and extended the survival time of mice, exhibiting a better effect than PD-1 NVs alone. The data also verified that the percentage of CD8+ T cells in tumors was highest after PD-1 @siNF90 NVs treatment. To sum up, PD-1 @siNF90 NVs could serve as safe and effective blockers in the treatment of melanoma.