Transarterial　chemoembolization　(TACE)　is　the　most　commonly　used　treatment　for　advanced　hepatocellular　carcinoma　(HCC),　but　still　lacks　accurate　real-time　biomarkers　for　monitoring　its　therapeutic　efficacy.　Here,　we　explored　whether　copy　number　profiling　of　circulating　free　DNA　(cfDNA)　could　be　utilized　to　predict　responses　and　prognosis　in　HCC　patients　with　TACE　treatment.　In　total,　266　plasma　cfDNA　samples　were　collected　from　64　HCC　patients,　57　liver　cirrhosis　(LC)　patients　and　32　healthy　volunteers.　We　performed　low-depth　whole-genome　sequencing　(LD-WGS)　on　cfDNA　samples　to　conduct　copy　number　variant　(CNV)　analysis　and　tumour　fraction　(TFx)　quantification.　Then,　the　correlation　between　TFx/CNVs　and　therapeutic　efficacy,　treatment　outcomes　and　lipiodol　deposition　were　explored.　The　change　in　TFx　during　TACE　treatment　was　associated　with　patients＇　tumour　burden,　and　could　accurately　and　earlier　predict　treatment　response　and　prognosis,　providing　an　alternative　strategy　other　than　mRECIST.　Meanwhile,　the　chromosomal　16q/NQO1　amplification　indicated　worse　therapeutic　response;　in　patients　who　underwent　multiple　TACE　sessions,　TFx　change　during　their　first　TACE　treatment　reflected　the　long-term　survival;　additionally,　the　copy　number　amplification　of　chromosome　1q,　3p,　6p,　8q,　10p,　12q,　18p　or　18q　affected　lipiodol　deposition.　Overall,　we　have　provided　a　new　liquid　biopsy　approach　for　future　TACE　management　of　HCC　patients.