We report the synthesis and biological evaluation of NSCA-1. NSCA-1 exerts synergistic cytotoxicity with Adriacin in HepG2-ADR cells. NSCA-1 significantly decreased the expression of p-Akt and p-GSK3β. NSCA-1enhanced the sensitivity of HepG2-ADR cells to Adriacin via P-gp inhibition. NSCA-1 enhanced Adriacin induced apoptosis via p53 dependent pathway.