Immune　cells　play　a　crucial　role　in　the　development　of　Hepatocellular　Carcinoma　(HCC),　with　mast　cells　displaying　unique　bidirectional　biological　characteristics.　This　study　aims　to　investigate　the　heterogeneity　of　hypertrophic　cells　in　HCC　and　their　impact　on　prognosis　and　potential　dual　roles.　We　performed　single-cell　RNA　sequencing　(scRNA-seq)　analysis　on　tumor　tissues　from　32　HCC　patients　and　adjacent　non-tumor　tissues　from　5　of　these　patients,　with　validation　through　multiplex　immunohistochemistry　(mIHC)　on　90　tumor　and　90　adjacent　tissues.　Additional　validation　was　done　using　public　datasets　(TCGA-LIHC,　GSE14520)　and　cellular　functional　assays.　Our　findings　reveal　a　mast　cell-specific　enrichment　in　tumor　tissues,　identifying　four　functionally　distinct　subpopulations　of　tumor-associated　mast　cells　(TAMCs):　Mast_1　(antigen-presenting),　Mast_2　(cholesterol　metabolism-associated),　Mast_3　(transcription　factor-enriched),　and　Mast_4　(oncogenic　and　prognostically　adverse).　Deconvolution　analysis　showed　significant　upregulation　of　TAMCs　signature　genes　(PSMB8,　APOE,　SOX4,　VEGFA),　and　transcriptional　network　analysis　highlighted　JUND,　NF-κB,　REL,　and　CREM　as　potential　co-regulators　of　Mast_2/Mast_4　differentiation.　mIHC　and　survival　analysis　indicated　that　high　apolipoprotein　E　(APOE)　expression　correlated　with　favorable　prognosis　(p　©　2025　Elsevier　B.V.