Aim To explore the effect of lncRNA PVT1 on oxidative stress and cardiomyocyte apoptosis induced by hypoxia/reoxygenation (H/R) and its regulatory effect on miR-761. Methods Rat cardiomyocyte H9c2 cells were treated with hypoxia and reoxygenation (H/R) to establish a cell injury model. si-NC, si-PVT1, miR-mimics-NC, miR-761 mimics, si-PVT1 and miR-inhibitor-NC, si-PVT1 and miR-761 inhibitor were transfected into H/R-induced cardiomyocytes. qRT-PCR method was used to detect the expression of PVT1 and miR-761. Flow cytometry was used to detect the apoptosis rate. The levels of malondialedhyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were detected by Kits. The dual luciferase reporter experiment was used to analyze the targeting relationship between PVT1 and miR-761. Western blot was used to detect the expression of Bcl-2 and Bax protein. Results Compared with the control group, the expression level of PVT1 in the H/R group was increased (P＜0.05), and the expression level of miR-761 was decreased (P＜0.05). Compared with the H/R＋si-NC group, the apoptosis rate and the protein level of Bax were decreased in the H/R＋si-PVT1 group (P＜0.05), the protein level of Bcl-2 and the activities of SOD and CAT were increased (P＜0.05), and the content of MDA was decreased (P＜0.05). Compared with H/R＋miR-mimics-NC group, the apoptosis rate and the protein level of Bax were decreased in H/R＋miR-761 mimics group (P＜0.05), the protein level of Bcl-2 and the activities of SOD and CAT were increased (P＜0.05), the content of MDA was decreased (P＜0.05). The result of dual luciferase report experiment confirmed that miR-761 was the downstream target of PVT1. Interference with miR-761 could obviously reverse the effect of silencing PVT1 on H/R-induced oxidative stress and apoptosis of cardiomyocytes. Conclusion Silencing PVT1 could inhibit H9c2 cell apoptosis and oxidative stress by up-regulating miR-761, thereby reducing H/R-induced cardiomyocyte damage.