Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent global health burden, yet the post-translational mechanisms governing hepatic lipid homeostasis remain incompletely defined. Here, we identify the depalmitoylase Abhd17a as a critical suppressor of hepatic steatosis through its regulation of the palmitoyl acyltransferase Zdhhc7. While Abhd17a deficiency alone does not induce overt pathology in wild-type mice, its genetic ablation in ApoE−/− mice markedly accelerates MASLD progression, characterized by enhanced steatosis, inflammation, fibrosis, and insulin resistance. Mechanistically, Abhd17a directly interacts with and depalmitoylates Zdhhc7 at evolutionarily conserved cysteine residues Cys160 and Cys166, whose autopalmitoylation is essential for Zdhhc7 Golgi retention and enzymatic activity. Loss of Abhd17a enhances Zdhhc7 autopalmitoylation, promoting CAV1 palmitoylation and the subsequent formation of a Cav1-Cd36 complex that augments hepatic lipid uptake without altering transcriptional programs. Thus, the Abhd17a-Zdhhc7-Cav1/Cd36 axis represents a critical post-translational checkpoint and a promising therapeutic target for MASLD.