To validate the potential of SPARC as a therapeutic target, we examined the effect of the knockdown of SPARC with SPARC-specific siRNA on the growth of human melanoma cell lines. SPARC siRNAs exerted a potent knockdown effect. Silencing of SPARC resulted in growth inhibition with G(1) arrest accompanied by accumulation of p21, a G(1) cyclin-dependent kinase inhibitor, in MeWo and CRL1579 cells. Moreover, the induction of p53 was observed in MeWo cells, but not in CRL1579 cells. Conditioned media containing SPARC from MeWo cells could not restore the growth of SPARC-silenced MeWo cells. This result suggests that intracellular SPARC, but not secreted SPARC, is involved in cell proliferation