The mammalian intestine harbors a mass of microorganisms that is essential to maintain intestinal epithelium homeostasis and health. However, some microbes can damage the epithelial mucosal barrier to utilize nutrients for their survival and growth. Autophagy is a highly conserved cellular process that targets cytoplasmic damaged organelles and some cellular molecules to lysosome for degradation. Accumulating studies have demonstrated that autophagy plays an important role in the innate immune system in response to different gut pathogens. For instance, autophagy can be induced to mediate the process of pathogenic infection during pathogens invasion. In this review, we mainly discuss the steps of autophagy pathway mediated by microbes and the role of autophagy in the gut pathogens clearance and evasion.