Fuzheng　Qingjie　(FZQJ)　recipe　is　a　polyherbal　Chinese　medicine　capable　of　suppressing　tumor　growth　and　is　used　as　an　adjuvant　therapy　for　various　types　of　cancer.　However,　its　anticancer　mechanisms　are　yet　to　be　fully　elucidated.　In　the　present　study,　we　explored　whether　p38　mitogen-activated　protein　kinase　(MAPK)　was　involved　in　FZQJ-mediated　mitochondriadependent　apoptosis　in　human　hepatocellular　carcinoma　cells.　3-(4,5-Dimethylthiazol-2-yl)-2,5-　diphenyltetrazolium　bromide　(MTT)　assays　were　used　to　measure　the　viability　of　HepG2　cells.　4,6-Diamidino-2-phenylindole　(DAPI)　and　Annexin-V　fluorescein　isothiocyanate　(FITC)　were　used　to　analyze　the　apoptosis　of　HepG2　cells.　The　mitochondrial　membrane　potential　(Δψ)　and　phosphorylated　P38　MAPK　protein　were　examined　by　a　flow　cytometer　following　5,5′,6,6′-　tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine　iodide　(JC-1)　and　Alexa　Fluor®　647　mouse　anti-phosphorylated　P38　MAPK　antibody　staining,　respectively.　The　activation　of　caspase-9　and　caspase-3　were　measured　using　colorimetric　assays.　Additionally,　Bcl-2　and　Bax　expression　were　examined　using　reverse　transcription　polymerase　chain　reaction　(RT-PCR)　and　western　blot　analysis.　The　results　demonstrated　that　water　extract　of　FZQJ　was　able　to　induce　apoptosis　of　HepG2　cells　in　vitro.　FZQJ-induced　apoptosis　was　accompanied　by　the　loss　of　Δψ,　downregulation　of　Bcl-2　and　upregulation　of　Bax　expression,　and　the　activation　of　caspase-3,　-9　and　P38　MAPK.　These　results　indicated　that　FZQJ　induced　apoptosis　in　HepG2　cells　at　least　via　P38　MAPK　activation　and　the　mitochondria-dependent　apoptotic　pathway.