The study investigated the relationship between HDL cholesterol level and metabolic dysfunction-associated steatotic liver disease (MASLD) in 14,280 Japanese patients. Research has shown an inverse correlation between HDL-C levels and the incidence of MASLD, with each increase in HDL-C being associated with a lower risk of the disease. The analysis revealed a non-linear relationship with a critical limit of HDL-C at the level of 1.04 mmol/l. Above this threshold, each unit increase in HDL-C resulted in a 61% decrease in the odds of MASLD (OR = 0.39). Below this critical level, this protective relationship was not confirmed. Thus, elevated HDL-C levels above 1.04 mmol/L significantly reduce the risk of MASLD in the Japanese population. These findings highlight the importance of maintaining optimal HDL cholesterol levels in preventing this disease.