In this study, we found that knockdown of SPARC expression could decrease the expressions of Cyclin D1 and PCNA and increase the expressions of P53 and P21, which suggested that depletion of SPARC could inhibit ovarian cancer cell proliferation through activation of a p53/p21Cip1/Waf1 pathway dependent to G1-S checkpoint. The gene discussed is CDKN1A; the disease is ovarian cancer.