Objective: To investigate the expression of miR-129 in high-grade serous ovarian cancer (HGSOC) tissues and cell lines, and to explore its effect on the invasion and migration of ovarian cancer cells and its mechanism. Methods: Real-time quantitative PCR (qRT-PCR) was used to detect the expression of miR-129 and HMGA2 in 70 HGSOC tissues and 30 normal fallopian tubes, and the expression of miR-129 in human ovarian cancer cell lines and human normal ovarian epithelial cells. Pearson correlation analysis evaluated the correlation between miR-129 and HMGA2 expression in HGSOC tissues. After transfection of ovarian cancer cells CAOV with a miR-129 mimic and control, cell invasion was detected by Transwell microscopy, cell migration was detected by cell scratch test, and HMGA2 mRNA and protein expression changes were detected. Bioinformatics software and luciferase reporter gene assay were used to analyze the targeting effect of miR-129 on HMGA2 gene. HMGA2 overexpression plasmid was transfected to observe the effect of HMGA2 on the invasion and migration of miR-129 mimic CAOV cells. Results: The expression of miR-129 in HGSOC tissues and cell lines were significantly lower than that in normal fallopian tubes and normal ovarian epithelial cells (P<0.05). HMGA2 was significantly higher in HGSOC tissues than in normal fallopian tubes (P<0.05), negatively correlated with the expression of miR-129 (r=−0.712, P<0.05). Compared with the control group, the invasion and migration ability of CAOV cells in miR-129 mimic group decreased, and the expression of HMGA2 mRNA and protein decreased (P<0.05); bioinformatics software prediction and luciferase reporter gene experiments confirmed that HMGA2 is a target gene of miR-129; compared with miR-129+ control group, miR-129 mimic+HMGA2 group has significantly increased invasion and migration ability (all P<0.05). Conclusion: MiR-129 is lowly expressed in HGSOC tissues, and it can inhibit the invasion and migration of ovarian cancer cells by targeting down-regulation of HMGA2.