Human herpesvirus 8 (HHV8) is the etiologic agent for primary effusion lymphoma (PEL). The aim of this study is to investigate the effects of cisplatin on the PEL cells. Cisplatin treatment induced apoptosis and inhibited the growth of PEL cells, and the effect was more profound in the HHV8-positive lymphoma cells compared with the EBV-positive lymphoma cells. Cisplatin treatment decreased the expression of HHV8 latent genes and activated p53 at serine 15 in PEL cells. Our results indicate that cisplatin can disrupt HHV8 latency and induce reactivation of p53 and highly selective treatment modality for this virally induced lymphoma.