Abstract: The overall cancer incidence and death toll have been increasing worldwide. However, the conventional therapies have some obvious limitations, such as non-specific targeting, systemic toxic effects, especially the multidrug resistance (MDR) of tumors, in which, autophagy plays a vital role. Therefore, there is an urgent need for new treatments to reduce adverse reactions, improve the treatment efficacy and expand their therapeutic indications more effectively and accurately. Combination therapy based on autophagy regulators is a very feasible and important method to overcome tumor resistance and sensitize anti-tumor drugs. However, the less improved efficacy, more systemic toxicity and other problems limit its clinical application. Nanotechnology provides a good way to overcome this limitation. Co-delivery of autophagy regulators combined with anti-tumor drugs through nanoplatforms provides a good therapeutic strategy for the treatment of tumors, especially drug-resistant tumors. Notably, the nanomaterials with autophagy regulatory properties have broad therapeutic prospects as carrier platforms, especially in adjuvant therapy. However, further research is still necessary to overcome the difficulties such as the safety, biocompatibility, and side effects of nanomedicine. In addition, clinical research is also indispensable to confirm its application in tumor treatment. Keywords: autophagy, tumor resistance, nanotechnology, combination therapy, co-delivery