Abstract: Malignant tumors are currently the main obstacle to prolonging life expectancy. Although chemotherapy is an important therapeutic measure for malignant tumors, a multidrug-resistant phenotype can be progressively induced in malignant tumors during chemotherapy, leading to poor prognosis. Multidrug resistance is reportedly associated with a number of mechanisms, including drug transport and absorption, apoptosis, and DNA damage repair. Recent studies have shown that protein glycosylation plays an important role in multidrug resistance in tumors. This article reviews molecular mechanisms by which protein glycosylation contributes to tumor multidrug resistance, which are expected to provide theoretical bases for clinically reversing multidrug resistance.