Macroautophagy (hereafter referred to as autophagy) is a conserved eukaryotic process, in which dysfunctional proteins, organelles, and other macromolecules are wrapped in intracellular vesicles called autophagosomes and delivered to lysosomes for degradation (Mizushima et al., 2008; Mizushima and Komatsu, 2011). Autophagy restores cellular energy and recycles cytoplasmic precursors, sustaining cell homeostasis and cell survival (Mizushima et al., 2008; Mizushima and Komatsu, 2011). Elevated autophagy can be detected in both cancer cells and surrounding stromal cells in pancreatic cancer (PC), affecting tumor initiation and progression as well (Yang et al., 2011; Endo et al., 2017). The role of autophagy in PC is highly context-dependent. Here, we illustrate the multifactorial role of autophagy in PC, and the significance of autophagy will be emphasized not only in cancer cells but also in the tumor microenvironment.