OBJECTIVE:To investigate the role of peroxidoxin 1 (Prx1) in thyroid cancer cell death induced by proteasome inhibitors. MESUTLS: The undifferentiated thyroid cancer FRO cells were treated with vehicle,proteasome inhibitor MG132,PSI and lactacystin; Prx1 expression levels were knockdown by RNA interference (RNAi); Prx1 mRNA and protein levels were analyzed by using real-time RT-PCR and Western blot,respectively; the apoptotic rate was analyzed by using flow cytometry (FCM). RESULTS: MG132,PSI and lactacystin significantly increased the mRNA and protein levels of Prx1 (P0.01) in undifferentiated thyroid cancer FRO cells; small interfering RNA against Prx1 (siPrx1) markedly reduced the Prx1 mRNA and protein levels when compared with vehicle or scramble siRNA (P0.01),in addition,siPrx1 dramatically increased MG132-,PSI- or lactacystin-mediated increase in apoptotic cells (P0.01). CONCLUSION: Proteasome inhibitors increase the Prx1 expression in undifferentiated thyroid cancer FRO cells,and the suppression of Prx1 expression by siPrx1 significantly enhances the apoptosis of FRO cells induced by proteasome inhibitors.