Objective：To explore the role and mechanism of piperlongumine in high calcium/phosphate-induced calcification of aortic valve interstitial cells（AVICs）. Methods：Porcine AVICs were isolated and cultured in vitro. AVICs were treated inductively with high calcium/phosphate medium and piperlongumine of different concentrations for 16 hours. Flow cytometry was then performed to measure cell apoptosis. AVICs were treated with 2.5 mmol/L piperlongumine or 100 ng/mL bone morphogenetic protein 2（BMP2）under the condition of high calcium/phosphate. The effect of piperlongumine on calcification was measured using calcium quantification，alkaline phosphatase activity and alizarin red staining. The protein and mRNA levels of osteogenic markers were determined by Western blot and real-time PCR. Results：①Flow cytometry showed that piperlongumine under 5 mmol/L had no obvious effect on AVICs apoptosis treated with high calcium/phosphate medium. ②Calcium quantification，alkaline phosphatase activity and alizarin red staining showed that 2.5 mmol/L piperlongumine attenuated the calcification of AVICs induced by high calcium/phosphate medium. ③Western blot，real-time PCR showed that 2.5 mmol/L piperlongumine inhibited the protein and mRNA expression of osteogenic markers including BMP2，phosphorylated Smad1/5 and RUNX2. ④Exogenous recombinant BMP2 may reverse the effect of piperlongumine in vitro. Conclusion：Piperlongumine attenuates high calcium/phosphate-induced AVICs calcification by inhibiting BMP2/pSmad1/5 signaling.