Lipid droplets (LDs) are cellular lipid storage organelles involved not only in lipid homeostasis but also in a variety of diseases. Chronic hepatitis C virus (HCV) infection affects host lipid metabolism, and thus induces LD accumulation in the liver. Recent studies have suggested that cellular LDs also play a crucial role in the HCV life cycle. Interactions between HCV proteins, especially the core protein, and LDs are required for the morphogenesis of infectious HCV. The present minireview will summarize the recent research progress about this unique relationship between LDs and the HCV life cycle.