Hepatic lipid metabolism is closely associated with certain diseases, such as obesity, diabetes, fatty liver, and hepatic fibrosis. Hepatic steatosis results from systemic metabolic dysfunction that occurs via multiple processes. The initial process has been characterized as hepatic lipid accumulation that may be caused by increased liver lipid uptake and de novo lipogenesis or decreased lipid oxidation and lipid export; subsequently, multiple additional factors that trigger inflammation and insulin resistance (IR) aggravate the progression of hepatic steatosis. Emerging evidence indicates that inflammation stands at the crossroads of innate immunity and lipid metabolism and links the initial metabolic stress and subsequent metabolic events in lipid metabolism. Therefore, in this review, we summarize the regulatory role of innate immune signaling molecules in maintaining lipid metabolic homeostasis; these revelations can guide the development of potential therapies for nonalcoholic fatty liver disease (NAFLD).