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It is unclear how fasting affects the tumor microenvironment (TME) and tumor\u2010targeted drug delivery. Here the effects of intermittent (IF) and short\u2010term (STF) fasting are investigated on tumor growth, TME composition, and liposome delivery in allogeneic hepatocellular carcinoma (HCC) mouse models. To this end, mice are\u00a0inoculated either subcutaneously or intrahepatically with Hep\u201055.1C cells and subjected to IF for 24 d or to STF for 1 d. IF but not STF significantly slows down tumor growth. IF increases tumor vascularization and decreases collagen density, resulting in improved liposome delivery. In vitro, fasting furthermore promotes the tumor cell uptake of liposomes. These results demonstrate that IF shapes the TME in HCC towards enhanced drug delivery. Finally, when combining IF with liposomal doxorubicin treatment, the antitumor efficacy of nanochemotherapy is\u00a0found to be increased, while systemic side effects are\u00a0reduced. 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