Low-temperature plasma (LTP) has emerged as a groundbreaking method for inducing immunogenic cell death (ICD) in cancer cells. ICD is a form of cellular demise that triggers an immune response against malignant cells. LTP has demonstrated remarkable potential in activating the immune system and augmenting antitumor responses. In this study, we delved into the capacity of LTP to induce ICD and explored its impact on the immune system. Additionally, we assessed the therapeutic effects of LTP-induced ICD on the immune system within a melanoma tumor model. The LTP treated B16F10 (LTP-B16) showed a notable surge in CD8+T cells accompanied by enhanced expression of granzyme B and IFN-γ, and reduction in Treg cells. This study ingeniously amalgamated LTP-induced ICD with cisplatin to synergistically impede tumor growth. These results offer fresh perspectives for the creation of tumor vaccines based on LTP as well as a new approach for therapeutic tumor immunotherapy.