The integrin α (ITGA) subfamily genes play a fundamental role in various cancers. However, the potential mechanism and application values of ITGA genes in adipogenic differentiation of human adipose-derived stem cells (hADSCs) remain elusive. This study confirmed that ITGA2/3/5 mRNA expressions were repressed during adipogenesis. Blockade of ITGA2/3/5 enhanced adipogenic differentiation of hADSCs. Oil red O staining found that more lipid droplets were apparent in the ITGA2/3/5 inhibition group following 14 d adipogenic induction than in the control group. In addition, inhibition of ITGA2/3/5 promoted the expression of adipogenesis-related genes (PPAR-γ, C/EBPα, FABP4). Mechanistically, ITGA2/3/5 functioned by regulating the Rac1 signaling pathway, which reasonably explains ITGA2/3/5's role in adipogenic differentiation of hADSCs. Our studies suggest that blockades of ITGA2/3/5 promote the adipogenic differentiation of hADSCs.