The invention relates to application of a histone deacetylase inhibitor to cell culture. The application is in-vitro directed differentiation culture of multipotential stem cells to liver cells or in-vitro culture of primary liver cells, wherein the histone deacetylase inhibitor is CI-994, MS-275 or FK228. The invention also provides an in-vitro directed differentiation culture system of the multipotential stem cells to liver cells as well as an in-vitro culture medium of the primary liver cells. According to the technical scheme provided by the invention, the quality of the liver cells obtained by differentiation can be remarkably promoted, and loss of liver features in the in-vitro culture process of the primary liver cells can be reduced.