Rationale:　Sma　mothers　against　decapentaplegic　homologue　4　(Smad4)　is　a　key　mediator　of　the　transforming　growth　factor　beta　(TGF-beta)　pathway　and　plays　complex　and　contradictory　roles　in　hepatocellular　carcinoma　(HCC).　However,　the　specific　role　of　Smad4　in　hepatocytes　in　regulating　hepatocarcinogenesis　remains　poorly　elucidated.　Methods:　A　diethylnitrosamine/carbon　tetrachloride-induced　HCC　model　was　established　in　mice　with　hepatocyte-specific　Smad4　deletion　(Alb(Smad　4-/-))　and　liver　tumorigenesis　was　monitored.　Immune　cell　infiltration　was　examined　by　immunofluorescence　and　fluorescence　activated　cell　sorting　(FACS).　Cytokine　secretion,　glycolysis,　signal　pathway,　and　single-cell　RNA　sequencing　were　analysed　for　mechanism.　Results:　Alb(Smad4-/-)　mice　exhibited　significantly　fewer　and　smaller　liver　tumor　nodules,　less　fibrosis,　reduced　myeloid-derived　suppressor　cell　infiltration　and　increased　CD8(+　)T　cell　infiltration.　Smad4　deletion　in　hepatocytes　enhanced　C-X-C　motif　ligand　10　(CXCL10)　secretion,　promoting　tumor　necrosis　factor-alpha　(TNF-alpha)　production　in　CD8(+)　T　cells.　The　loss　of　Smad4　activated　the　CXCL10/mammalian　target　of　rapamycin　(mTOR)/lactate　dehydrogenase　A　(LDHA)　pathway,　which　increased　glycolytic　activity　in　CD8(+　)T　cells.　HCC　patients　with　high　Smad4　expression　exhibited　decreased　CD8(+)　T　cell　infiltration　and　altered　glycolysis.　Conclusion:　Our　results　demonstrate　that　Smad4　in　hepatocytes　promotes　hepatocarcinogenesis　and　is　a　potential　and　candidate　target　for　the　prevention　and　therapy　of　HCC.