Increasing evidence has suggested that dysregulation of microRNAs (miRNAs) could contribute to tumor progression. The miR-125a was downregulated in several types of cancer; however, the molecular mechanism of miR-125a in the ovarian cancer remains unclear. The aim of the paper was to study the expression of miR-125a in ovarian cancer and miR-125a's relation to the cell proliferation and invasion in ovarian cancer. In this study, we demonstrated that miR-125a is downregulated in ovarian cancer tissues and cell lines, compared with the corresponding adjacent non-neoplastic tissues and normal human fallopian tube epithelial cell line. Histone deacetylase 4 (HDAC4), which has been reported to be associated with invasive ovarian cancer, was identified as a novel target of miR-125a in OVCAR-3 ovarian cancer cells, and the protein expression of HDAC4 was negatively regulated by miR-125a in OVCAR-3 cells. Additionally, upregulation of miR-125a and downregulation of HDAC4 suppressed ovarian cancer cell proliferation and invasion. These data suggest that miR-125a may suppress ovarian cancer cell proliferation and invasion through direct inhibition of HDAC4 expression. Taken together, our findings show that miR-125a functions as tumor suppressor in ovarian cancer by targeting HDAC4, and miR-125a may therefore serve as a biomarker for diagnosis and therapeutics in ovarian cancer.