Plasma with low temperature generated at atmospheric pressure is known as cold atmospheric plasma (CAP). Owing to its unique characteristics and biological effects of inducing tumor cell death without endangering the surrounding healthy tissues, CAP is regarded as an emerging potent anticancer strategy and has been extensively investigated in preclinical research. In this review, we define the reactive species that play a major role in CAP as a novel “drug” (termed as plasma drug) used in cancer therapy. Various methods of plasma drug use in tumor treatment were summarized, mainly including plasma drug direct delivery, carriers for plasma drug, plasma drug synergistic immunotherapy, plasma drug in combination with nanoparticle therapy, plasma drug delivery with other anti-tumor drugs, and biomedical devices assisted plasma drug delivery. Furthermore, we provide prospective on the future development of plasma drug for cancer therapy. Plasma drug has the potential to evolve into a novel class of cancer therapy with continued technology improvements and multidisciplinary research efforts, providing patients with effective and individualized treatment alternatives (Scheme [1](#fig-cap-0001)).