Aim To analyze the relationship between the effect of bile acid reducing the level of apolipoprotein A (ApoA) and the expression of miR-23b-3p, and to find new mechanisms of bile acid reducing the level of ApoA. Methods The target genes of miR-23b-3p and transcription factor hepatocyte nuclear factor 4γ (HNF4γ) regulating the LPA gene were analyzed by bioinformatics online tools Targetscan 7.0. Luciferase reporter assay was used to test target gene relationship for miR-23b-3p. Protein expression of ApoA, mitogen-activated protein kinase (p38MAPK) and p-p38MAPK were detected by Western blot in HepG2 cells, and miR-23b-3p expression was measured by real-time quantitative polymerase chain reaction. Results Bioinformatics analysis indicated that HNF4γ could act as a target gene of miR23b-3p. The fluorescent intensity of miR-23b-3p transfection cells was significantly lower than that of control group by using luciferase report assay, and it meant that HNF4γ could act as a target gene of miR23b-3p. Bile acid restrained ApoA expression in HepG2 cells in a dose- and time-dependent manner, and 32 mg/L and 24 h were the best action dose and time. Bile acid restraining the ApoA expression was related to the activation of MAPK and the up-regulation of miR-23b-3p. Moreover, it could regulate the expressions of miR-23b-3p, farnesyl X receptor and MAPK. Conclusion Bile acid can significantly down-regulate ApoA expression in HepG2 cells by a dose- and time-dependent manner, its mechanism is related to up-regulating the expression of miR-23b-3p.