Human adipose-derived stem cells (hASCs) improve renal function in acute kidney injury. Hypoxia-inducible factor-1 alpha (HIF-1 alpha) was transfected into hASCs. hASCs modified by lentivirus-mediated empty-vector and HIF-1 alpha maintained their stem cell characteristics. The expression of the renal-protective gene, heme oxygenase-1 and vascular endothelial growth factor were significantly increased in hASCs modified by HIF-1 alpha, compared to hASCs modified by empty-vector. Cellular ultra-structure and TUNEL staining revealed that hASCs modified by HIF-1 alpha promoted the recovery of apoptotic morphology in cisplatin-treated human kidney-2 cells (HK-2 cells) when compared to hASCs modified by empty-vector. Additionally, hASCs modified by empty-vector inhibited caspase-3 expression and up-regulated Bcl-2 expression in cisplatin-treated HK-2 cells, an effect even more pronounced with hASCs modified by HIF-1 alpha. Thus, HIF-1 alpha gene-modified ASCs could be an effective way to enhance the renal-protective effect.