AXL is a member of TAM (TYRO3-AXL-MER) family of receptor tyrosine kinases, which is overexpressed in many cancers, including non-small cell lung cancer, breast cancer and ovarian cancer. It can mediate the occurrence of epithelial-mesenchymal transition, and plays an important role in tumor drug resistance. In addition, AXL can also mediate the occurrence of targeted agents resistanceregulating the signaling pathway and influencing tumor microenviroment. As a result, AXL is an attractive candidate not only as a prognostic indicator in malignancy but also as a target for anti-cancer therapy. Several multi-target small molecule inhibitors against AXL have been approved, and varieties of inhibitors with higher specificity are in clinical or preclinical studies. This article focused on the role of AXL in tumor drug resistance and summarized the research profiles of different small molecule inhibitors against AXL to provide new ideas for anti-tumor research and therapy.