Hepatocellular　carcinoma　is　the　third　leading　cause　of　deaths　from　cancer　worldwide.　Infection　with　the　hepatitis　B　virus　is　one　of　the　leading　risk　factors　for　developing　hepatocellular　carcinoma,　particularly　in　East　Asia(1).　Although　surgical　treatment　may　be　effective　in　the　early　stages,　the　five-year　overall　rate　of　survival　after　developing　this　cancer　is　only　50-70%(2).　Here,　using　proteomic　and　phospho-proteomic　profiling,　we　characterize　110　paired　tumour　and　non-tumour　tissues　of　clinical　early-stage　hepatocellular　carcinoma　related　to　hepatitis　B　virus　infection.　Our　quantitative　proteomic　data　highlight　heterogeneity　in　early-stage　hepatocellular　carcinoma:　we　used　this　to　stratify　the　cohort　into　the　subtypes　S-I,　S-II　and　S-III,　each　of　which　has　a　different　clinical　outcome.　S-III,　which　is　characterized　by　disrupted　cholesterol　homeostasis,　is　associated　with　the　lowest　overall　rate　of　survival　and　the　greatest　risk　of　a　poor　prognosis　after　first-line　surgery.　The　knockdown　of　sterol　O-acyltransferase　1　(SOAT1)-high　expression　of　which　is　a　signature　specific　to　the　S-III　subtype-alters　the　distribution　of　cellular　cholesterol,　and　effectively　suppresses　the　proliferation　and　migration　of　hepatocellular　carcinoma.　Finally,　on　the　basis　of　a　patient-derived　tumour　xenograft　mouse　model　of　hepatocellular　carcinoma,　we　found　that　treatment　with　avasimibe,　an　inhibitor　of　SOAT1,　markedly　reduced　the　size　of　tumours　that　had　high　levels　of　SOAT1　expression.　The　proteomic　stratification　of　early-stage　hepatocellular　carcinoma　presented　in　this　study　provides　insight　into　the　tumour　biology　of　this　cancer,　and　suggests　opportunities　for　personalized　therapies　that　target　it.