Hepatocellular　carcinoma　(HCC)　is　one　of　the　most　aggressive　malignancies　worldwide,　and　its　incidence　associated　with　viral　infection　has　increased　in　recent　years.　Amantadine　is　a　tricyclic　symmetric　amine　that　can　effectively　protect　against　the　hepatitis　C　virus.　However,　its　antitumor　properties　remain　unclear.　In　the　present　study,　the　effects　of　amantadine　on　tumor　cell　viability,　cell　cycle　regulation　and　apoptosis　were　investigated.　The　growth　of　HepG2　and　SMMC-7721　cells　(HCC　cell　lines)　was　detected　by　an　MTT　assay.　Flow　cytometry　was　used　to　investigate　cell　cycle　regulation　and　apoptosis.　Reverse　transcription-quantitative　polymerase　chain　reaction　and　western　blot　analysis　were　also　performed　to　examine　the　expression　of　cell　cycle-　and　apoptosis-related　genes　and　proteins,　including　cyclin　E,　cyclin　D1,　cyclin-dependent　kinase　2　(CDK2),　B-cell　lymphoma　2　(Bcl-2)　and　Bax.　Our　results　demonstrated　that　amantadine　markedly　inhibited　the　proliferation　of　HepG2　and　SMMC-7721　cells　in　a　dose-　and　time-dependent　manner　and　arrested　the　cell　cycle　at　the　G0/G1　phase.　The　levels　of　the　cell　cycle-related　genes　and　proteins　(cyclin　D1,　cyclin　E　and　CDK2)　were　reduced　by　amantadine,　and　apoptosis　was　significantly　induced.　Amantadine　treatment　also　reduced　Bcl-2　and　increased　the　Bax　protein　and　mRNA　levels.　Additionally,　Bcl-2/Bax　ratios　were　lower　in　the　two　HCC　cell　lines　following　amantadine　treatment.　Collectively,　these　results　emphasize　the　role　of　amantadine　in　suppressing　proliferation　and　inducing　apoptosis　in　HCC　cells,　advocating　its　use　as　a　novel　tumor-suppressive　therapeutic　candidate.