Apoptin,　a　small　protein　derived　from　the　chicken　anemia　virus,　specifically　induces　apoptosis　in　transformed　cells　or　tumor　cells　but　not　in　normal　cells.　Thus,　apoptin　is　involved　in　a　general,　tumor-specific　pathway.　Apoptin-induced　apoptosis　presumably　requires　additional　interaction　partners　that　activate　specific　signaling　pathways　in　cancer　cells.　A　number　of　molecules　interact　with　apoptin　and　play　an　important　role　in　the　nuclear　localization　of　apoptin　or　its　tumor-selective　cytotoxicity.　Our　data　indicated　that　apoptin　selectively　kills　HepG2　hepatocellular　carcinoma　(HCC)　cells　but　has　no　effect　on　the　normal　liver　cell　line　HL-7702.　Analyses　of　human　HCC　tissue　samples　confirmed　that　CDK1　(cyclin-dependent　kinase　1)　activity　was　detected　in　primary　malignancies　but　not　in　healthy　paraneoplastic　tissues.　shRNA　knockdown　of　CDK1　significantly　reduced　the　tumor-specific　killing　effects　of　apoptin,　suggesting　that　CDK1　plays　an　important　role　in　the　regulation　of　apoptin-induced　apoptosis.　Furthermore,　the　majority　of　apoptin　translocated　to　the　cytoplasm　from　the　nucleus　after　knockdown　of　CDK1.　Collectively,　our　results　revealed　for　the　first　time　that　apoptin　interacts　with　CDK1　in　the　complex　process　of　tumorigenesis.　The　link　between　CDK1　and　apoptin　may　be　a　novel　cellular　signaling　pathway　to　modulate　apoptosis　in　cancer;　therefore,　apoptin　may　have　pharmacological　potential　to　be　directly　employed　for　cancer　therapy.