Objective To investigate the effects of remifentanil on the proliferation, apoptosis and oxidative stress of PC12 cells induced by hypoxia/reoxygenation and related molecular mechanisms. Methods According to the random number table method, PC12 cells were divided into the following groups (n=9): a hypoxia/reoxygenation group (hypoxia for 15 h followed by reoxygenation for 5 h), a blank group (normally cultured cells), remifentanil low, medium and high concentration groups (PC12 cells exposed to 2, 10, and 50 mg/L remifentanil after hypoxia/reoxygenation induction), a remifentanil+LY294002 group (PC12 cells exposed to 10 mg/L remifentanil and 50 μmol/L LY294002 after hypoxia/reoxygenation induction), and a remifentanil+PBS group (PC12 cells exposed to 10 mg/L remifentanil and an equal amount of phosphate buffer saline after hypoxia/reoxygenation induction). The levels of cyclin D1, cleaved cysteinyl aspartate specific proteinase‑3 (cleaved caspase‑3), B‑cell lymphoma‑2 related X protein (Bax), B‑cell lymphoma‑2 (Bcl‑2), phosphorylated protein kinase B (p‑Akt), phosphorylated mammalian target of rapamycin (p‑mTOR), and phosphorylation signal transduction and transcriptional activator 3 (p‑STAT3) were detected by Western blot. The cell viability was measured by tetramethylazozolium salt colorimetric assay (MTT) assay. The apoptosis was examined by flow cytometry. Reactive oxygen species (ROS) kits and superoxide dismutase (SOD) kits were used to detect ROS levels and SOD activity in the blank group, the hypoxia/reoxygenation group, and the remifentanil low, medium, and high concentration groups, respectively. The levels of interleukin‑1β (IL‑1β) and tumor necrosis factor‑α (TNF‑α) were detected by enzyme‑linked immuno sorbent assay (ELISA). Results Compared with the blank group, the levels of cyclin D1, Bcl‑2, p‑Akt, p‑mTOR and p‑STAT3, SOD activity and cell survival rate in the hypoxia/reoxygenation group significantly decreased; and the levels of cleaved caspase‑3, Bax, IL‑1β and TNF‑α, cell apoptosis rate and ROS fluorescence intensity in the hypoxia/reoxygenation group significantly increased (P<0.05). Compared with te hypoxia/reoxygenation group, the levels of cyclin D1, Bcl‑2, p‑Akt, p‑mTOR and p‑STAT3, cell survival rate and SOD activity in PC12 cells in the remifentanil low, medium and high concentration groups significantly increased; and the levels of cleaved caspase‑3, Bax, IL‑1β and TNF‑α, cell apoptosis rate and ROS fluorescence intensity significantly decreased (P<0.05). Compared with the remifentanil+PBS group, the levels of cleaved caspase‑3, Bax, IL‑1β and TNF‑α, and apoptosis rate in the remifentanil+LY294002 group significantly increased; and the levels of Bcl‑2, p‑Akt, p‑mTOR and p‑STAT3 and cell survival rate significantly decreased (P<0.05). Conclusions Remifentanil can stimulate the proliferation of PC12 cells, inhibit hypoxia‑reoxygenation‑induced apoptosis, oxidative stress and the secretion of inflammatory factors, which may be related to the protein kinase B/mammalian target of rapamycin/signal transducers and activators of transcription 3 (Akt/mTOR/STAT3) signaling pathway.