Objective：To determine the expression level of vacuolar protein sorting 13 homolog A（VPS13A）during cell differentiation of 3T3-L1 and to explore the effects of VPS13A on 3T3-L1 cells. Methods：Western blot and Q-PCR were used to detect the expression changes of VPS13A during the differentiation of 3T3-L1 cells，and CRISPR（clustered regularly interspaced short palindromic repeats）/Cas9（CRISPR associated with 9）system to establish stable VPS13A knowdown cell lines. Finally，the effect of VPS13A knockdown on 3T3-L1 cell differentiation was detected by Western blot and Oil red staining. Results：The expression of VPS13A was downregulated in the early stage and upregulated in the later stage of 3T3-L1 cell differentiation. Lipid droplets and the expression levels of genes involved in differentiation were increased in VPS13A knockdown 3T3-L1 cells. Conclusion：VPS13A expression is modulated by cell differentiation status in 3T3-L1 cells. Knockdown of VPS13A enhances the differentiation of 3T3-L1 cells.