Objective: To discuss the role and mechanism of propofol in cerebral ischemia-reperfusion injury. Methods: The cerebral ischemia-reperfusion model was produced by oxygen glucose deprivation and reperfusion in vitro, MTT assay was used to detect the proliferative effect of propofol; Apoptotic cells were detected with Annexin V staining; mRNA of bFGF was measured by RT-PCR; The effects of propofol on bFGF, pAKT and pERK1/2 protein expression was detected by Western blotting; Silence of bFGF in cortical neurons by small interfering RNA. Results: Propofol could significantly promote the viability of neurons and inhibit cell apoptosis after ischemia reperfusion injury. The expression of bFGF protein in OGD treated group was significantly lower than the control group (P<0.05), and the bFGF level was markedly upregulated in propofol treated group (P<0.05). Propofol could upregulate the expression of pAKT and pERK1/2, and activate the two signaling pathways. Silence the expression of bFGF or treatment with the inhibitor of PI3K-AKT and ERK1/2 signal pathway both resulted in the decrease of neurons viability (P<0.05), and the inhibition of PI3K-AKT and ERK1/2 activation. Conclusion: Propofol could activate PI3K-AKT and ERK1/2 signal pathway via upregulating the expression of bFGF, and promote the survival of cortical neurons.