AIM:　To　investigate　the　effects　of　guggulsterone　on　the　proliferation　and　apoptosis　of　human　hepatoma　HepG2　cells　in　vitro　and　relevant　mechanisms.　METHODS:　Human　hepatocellular　carcinoma　HepG2　cells　and　normal　human　liver　L-02　cells　were　treated　with　different　concentrations　of　guggulsterone　(5-100　mu　mol/L)　for　24-72　h.　Cell　proliferation　was　tested　by　MTT　assay.　Cell　cycle　and　apoptosis　were　investigated　using　flow　cytometry　(FACS).　Bcl-2　and　Bax　mRNA　and　protein　expression　was　detected　by　real-time　PCR　and　Western　blot,　respectively.　TGF-beta　1,　TNF-alpha,　and　VEGF　contents　were　determined　by　ELISA.　RESULTS:　Guggulsterone　significantly　inhibited　HepG2　cell　proliferation　in　a　dose-　and　time-dependent　manner.　FACS　showed　that　guggulsterone　arrested　HepG2　cell　cycle　at　G0/G1　phase.　Guggulsterone　induced　apoptosis　was　also　observed　in　HepG2　cells,　with　24.91%　+/-　2.41%　and　53.03%　+/-　2.28%　of　apoptotic　cells　in　response　to　the　treatment　with　50　mu　mol/L　and　75　mu　mol/L　guggulsterone,　respectively.　Bax　mRNA　and　protein　expression　was　significantly　increased　and　Bcl-2　mRNA　and　protein　expression　was　decreased.　ELISA　analysis　showed　that　the　concentrations　of　TGF-beta　1　and　VEGF　were　significantly　decreased　and　TNF-alpha　concentration　was　increased.　CONCLUSION:　Guggulsterone　exerts　its　anticancer　effects　by　inhibiting　cell　proliferation　and　inducing　apoptosis　in　HepG2　cells.　Guggulsterone　induces　apoptosis　by　activation　of　the　intrinsic　mitochondrial　pathway.