Recent studies have demonstrated overexpression of osteopontin (OPN) in ovarian clear cell carcinoma. Here, we revealed the role of OPN in invasiveness in ovarian clear cell carcinoma. We used immunofluorescence analysis to detect OPN in a total of 160 patient-derived specimens. Ovarian clear cell carcinoma cell lines, RMG-1 and TOV-21G, were used to monitor changes in OPN and integrin levels, and cell invasiveness following treatment with OPN, simvastatin, and transfection with siRNA. Immunofluorescence analysis revealed statistically significant differences among the histological groups, and ovarian clear cell carcinoma expressed a strong OPN signal. The OPN receptors, alpha v and 5, and beta 1 and 3 integrins, were increased after treatment with OPN. Invasion assays indicated that OPN enhanced in vitro extracellular matrix invasion dose-dependently in ovarian clear cell carcinoma. Simvastatin significantly reduced expression of OPN and the integrins, and decreased ECM invasion. RNA interference also suppressed ECM invasion. These results suggest that down- or up-regulation of OPN is involved in carcinoma cell invasion. We thus conclude that OPN regulation could have a crucial role in ovarian clear cell carcinoma therapy.