Abstract Autophagy is an important lysosomal degradation process that digests and recycles bio-molecules, protein or lipid aggregates, organelles, and invaded pathogens. Autophagy plays crucial roles in regulation of metabolic and oxidative stress and multiple pathological processes. In cancer, the role of autophagy is dual and paradoxical. Ubiquitination has been identified as a key regulator of autophagy that can influence various steps in the autophagic process, with autophagy-related proteins being targeted for ubiquitination, thus impacting cancer progression and the effectiveness of therapeutic interventions. This review will concentrate on mechanisms underlying autophagy, ubiquitination, and their interactions in cancer, as well as explore the use of drugs that target the ubiquitin-proteasome system (UPS) and ubiquitination process in autophagy as part of cancer therapy.