Objective To investigate the effect of PRF on proliferation, apoptosis and alkaline phosphatase activity of human dental pulp stem cells. Methods Human dental pulp stem cells (hDPSCs) were isolated from human dental pulp tissue, and were randomly divided into control group and experimental group. Cells in experimental group were co-incubated with PRF for 7 days. Cell proliferation and apoptosis were detected by CCK8 assay and flow cytometry on day 0, 1, 3, 5 and 7, respectively. Expression of alkaline phosphatase, Cleaved Caspase-3, p38 and p-p38 were measured by RT-PCR and Western blotting on day 0, 3, 7, 14. Results Cell proliferation was enhanced significantly on day 3, 5 and 7 compared with control group (P < 0.01). Expression of alkaline phosphatase were increased significantly on day 7 and 14 when compared with that in control group (P < 0.01). Cells apoptosis rate and expression of cleaved Caspase-3 were decreased while expression of p-p38 was increased significantly compared with those in control group (P < 0.01). No significant difference in p38 protein was observed between the two groups (P > 0.05). Conclusion PRF promotes the proliferation and inhibits the apoptosis of hDPSCs cells through mediation of p38 signaling pathway.