Abstract: OBJECTIVE To summarize the mechanism of antineoplastic drug resistance and explore the clinical treatment strategies. METHODS Retrieval of relevant literatures published in PubMed, Medline, Cochrane Library, CJFD, VIP and Wanfang databases on drug resistance and clinical treatment strategies of antineoplastic drugs was conducted, and the current use of antineoplastic drugs was reviewed. RESULTS The generation of antineoplastic drug resistance was influenced by many factors, such as the increase of drug efflux, the decrease of drug concentration in tumor cells, the enhancement of detoxification, the increase of DNA repair and damage function, the abnormal signal of tumor cell channels, and the change of target, et al. CONCLUSION Clinical treatment can be targeted according to the different mechanisms of drug resistance. Traditional Chinese medicine has multi-target effect, and its reversal of drug resistance has prominent advantages.