MicroRNAs (miRNAs) function as critical regulators of gene expression and their deregulation is associated with the development and progression of various cancers. This study aimed to investigate the biological role and mechanism of miR-205 in ovarian cancer (OC). MiR-205 was upregulated in OC tissues and cells in comparison to the controls. Meanwhile, overexpression of miR-205 was significantly associated with poor overall survival of OC patients. Functional study indicated that ectopic expression of miR-205 significantly promoted cell proliferation, migration, invasion and chemoresistance of OC cells. SMAD4 and PTEN were identified as direct targets of miR-205 using luciferase reporter assays, real-time PCR (qRT-PCR), and western blot. Most interestingly, in vivo studies indicated that miR-205 markedly promoted the growth and metastasis of tumors and the expression of miR-205 was also found to be inversely correlated with that of SMAD4 and PTEN in nude mice. Overall, we suggest that miR-205 functions as an oncogenic miRNA by directly binding to SMAD4 and PTEN, providing a novel target for the molecular treatment of ovarian cancer.