The usage of typical pharmaceuticals and personal care products (PPCPs) such as cardiovascular and lipid-modulating drugs in clinical care accounts for the largest share of pharmaceutical consumption in most countries. Atorvastatin (ATV), one of the most commonly used lipid-lowering drugs, is frequently detected with lower concentrations in aquatic environments owing to its wide application, low removal, and degradation rates. However, the adverse effects of ATV on non-target aquatic organisms, especially the molecular mechanisms behind the toxic effects, still remain unclear. Therefore, this study investigated the potentially toxic effects of ATV exposure (including environmental concentrations) on yellowstripe goby (Mugilogobius chulae) and addressed the multi-dimensional responses. The results showed that ATV caused typical hepatotoxicity to M. chulae. ATV interfered with lipid metabolism by blocking fatty acid β-oxidation and led to the over-consumption of lipids. Thus, the exposed organism was obliged to alter the energy supply patterns and substrates utilization pathways to keep the normal energy supply. In addition, the higher concentration of ATV exposure caused oxidative stress to the organism. Subsequently, M. chulae triggered the autophagy and apoptosis processes with the help of key stress-related transcriptional regulators FOXOs and Sestrins to degrade the damaged organelles and proteins to maintain intracellular homeostasis.