This study aimed to elucidate the underlying mechanisms for the protective effect of Lactobacillus on hypercholesterolemia. Firstly, twenty Lactobacillus strains were screened for potential probiotics with high bile salt hydrolase (BSH) activity using in vitro methods. Secondly, hypercholesterolemic mice induced by a cholesterol-enriched diet were administrated by the probiotic candidate strain L. plantarum Y15, identified from the screen. Results in vitro showed that L. plantarum Y15 possessed high BSH activity. In vivo, L. plantarum Y15 supplementation decreased total cholesterol and triglyceride in serum and liver, increased total cholesterol and total bile acid in feces, and alleviated histopathological changes in the liver. Furthermore, L. plantarum Y15 supplementation modulated the gut microbiota to the control group's pattern, leading to increase BSH activity, which further influence FXR and SHP signaling pathway to upregulate the expression level of CYP7A1 to enhance the cholesterol catabolism.