Autophagy is a highly conserved phenomenon of cell biology, and it is closely related to many major human diseases such as cancer, neurodegenerative diseases, and diabetes. Autophagy is a continuous biological process, including the formation of autophagosomes, the fusion of autophagosomes and lysosomes, the degradation of substrates, and the regeneration of lysosomes. Relative to the stage of autophagosome formation, there are fewer studies on some of the late processes such as the autophagosome-lysosome fusion phase, although some recent advances have been made. Nanoparticles such as silicon and polymeric nanoparticles are being increasingly applied in the electronic and pharmaceutical industries. Recent studies have revealed their role in autophagy and their cytotoxicity. In this review we summarize the current main findings of the molecular mechanisms of the autophagosome-lysosome fusion process and discuss several types of exogenous factors and their impacts on the fusion including protein products of pathogens and nanoparticles. In addition, we indicate remaining questions that need to be addressed in future studies separately in each section.