Agaricus subrufescens (AS) is a medicinal mushroom with notable bioactivity and the capacity to accumulate trace elements. In this study, selenium-enriched A. subrufescens (SAS) was cultivated, and its protective effects against alcoholic liver disease (ALD) were investigated, with an emphasis on clarifying the underlying mechanisms. The results showed that the yield and antioxidant capacity of mushrooms in a 10 mg·kg⁻¹ Se treatment group were increased. Nutritional analysis revealed that SAS contained considerable levels of crude protein (350.00 g·kg⁻¹), crude fiber (7.8%), free amino acids (250.20 g·kg⁻¹), and other bioactive constituents. Furthermore, the hepatoprotective effects of AS/SAS were studied in male Kunming mice with alcohol-induced liver injury. The body growth, liver index, serum and liver biochemical parameters, histopathological features of liver, hepatic mRNA levels and liver metabolomics were investigated. The results demonstrated that SAS significantly reduced hepatic lipid accumulation, enhanced antioxidant capacity, regulated the mRNA expression of key genes involved in lipid metabolism, oxidative stress, and inflammatory responses, and modulated liver metabolic characteristics. These findings provide theoretical evidence for the potential of SAS as a functional food against alcohol-induced liver injury.