Abstract: Anlotinib is a new anti-tumor small-molecule drug independently developed by China, which has achieved good curative effect in the clinical trials of a variety of tumors. During chemotherapy, drug resistance and sensitivity are directly related to the success or failure of the tumor’s drug treatment. The expression level of the tumor genes changes under the selection of anlotinib, which then causes changes in the signaling pathways to induce the tumor’s drug resistance. While the inhibition of the genes associated with the mechanisms of anlotinib resistance or the combination of other antitumor agents can improve the tumor’s sensitivity to anlotinib. This article summarizes the relevant studies on the resistance and sensitivity mechanism of anlotinib in vitro, and reviews the clinical reports of anlotinib in combination with PD-1/PD-L1 inhibitors to reverse anlotinib resistance, in order to provide a reference for the study of anlotinib resistance mechanism and clinical application.