Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. Increasing evidence reveals that PCOS may be associated with an increased level of oxidative stress. This study aimed to explore the role and potential mechanism of microRNA-873-5p (miR-873-5p) in PCOS. Quantitative real time-PCR (qRT-PCR) analysis was performed to evaluate the miR-873-5p levels in both clinical follicular fluid samples from patients with PCOS and cultured human ovarian granulosa cell-like KGN cells. The results indicated that miR-873-5p was up-regulated in the follicular fluid from patients with PCOS, as well as in the LPS-induced KGN cells. MTT assay showed that miR-873-5p inhibitor attenuated the LPS-induced inhibition of KGN cell viability. Flow cytometry indicated that miR-873-5p inhibitor suppressed cell apoptosis in LPS-induced KGN cells. Besides, miR-873-5p inhibitor resulted in a decrease in oxidative stress, which was evidenced by the reduced production of reactive oxygen species (ROS) and malondialdehyde (MDA). Further luciferase reporter assay proved that miR-873-5p directly targeted the 3′UTR of HO-1 mRNA. Small-interfering RNA (siRNA) targeting heme oxygenase-1 (HO-1) attenuated the effect of miR-873-5p inhibitor on oxidative stress in KGN cells. Besides, we also found that miR-873-5p inhibitor activated the p38/Nrf2/HO-1 signaling pathway in KGN cells. The findings may provide insightful evidence for preventing and treating PCOS by targeting miR-873-5p.