Obesity-associated hepatic steatosis is an important hepatic manifestation of obesity-related metabolic dysfunction, characterized by excessive hepatic lipid accumulation and closely associated with metabolic disturbances and increased risk of liver injury. Low-intensity pulsed ultrasound (LIPUS) is a non-invasive physical stimulation modality that has shown potential regulatory effects on metabolic homeostasis and inflammatory responses. However, the effects of LIPUS on obesity-associated hepatic steatosis and the associated hepatic proteomic alterations remain insufficiently understood. In this study, a high-fat diet-induced obese mouse model was established, and liver tissues were collected after LIPUS intervention. A mass spectrometry-based 4D-HT DIA quantitative proteomic approach was applied to systematically characterize hepatic proteomic alterations following LIPUS treatment. This dataset provides molecular profiling resources for investigating hepatic responses to LIPUS intervention in obesity-associated hepatic steatosis and supports further exploration of the underlying biological mechanisms.