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Transmissible spongiform encephalopathies (TSEs) belong to prion diseases that are invariably common fatal neurological disorders and affect humans and animals. Prion protein (PrP) was regarded as the only infectious agent inprion diseases and much attention was focused on the safety of PrP in foodstuffs. In this review, theprogress on the safety of milk relation to PrP and transmission route of prion diseases through milk are reviewed, including the discovery, content, source and the risk assessment of PrP in milk and milk products. And some possible control ways were proposed, which might be of particular interest for the improvement of milk safety relation to PrP in dairy food.