Accompanied with more elaborate and deeper exploration, immunotherapy has been considered one of the most important therapeutic manners for tumor treatment besides conventional operative, chemotherapeutic, radiotherapeutic and targeted-therapeutic strategies. The application of programmed death-1 (PD-1) antibody has provided a new therapeutic option for patients and becomes a research focus of immunotherapy field. PD-1 antibody has been permitted to apply to the treatment of different types of cancers such as melanoma. PD-1 has been demonstrated to be highly effective, including the steady tumor growth control, even complete remission acquired. Although the PD-1 antibody displays great therapeutic effectiveness and application prospects, an increasingly number of drug resistant phenomena have also occurred. Little has been known about the mechanisms of PD-1 antibody resistance by now. However, exploring this mechanism, innovating new treatment mode of drug combination, avoiding the occurrence of drug resistance and decreasing the adverse influence of drug resistance, even reversing it, will be useful to guide the adjustment of treatment strategies, continuously improve the effects of immunotherapy, and give patients long-term survival benefit.