Aberrant expression of genes in de novo lipogenesis (DNL) pathway were associated with various cancers,including hepatocellular carcinoma (HCC). Single nucleotide polymorphisms (SNPs) of DNL genes have beenreported to be associated with prognosis of some malignancies. However, the effects of SNPs in DNL genes onoverall survival of HCC patients receiving transarterial chemoembolization (TACE) treatment are still unknown.In present study, nine SNPs in three genes (ACLY, ACACA and FASN) in DNL pathway were genotyped usingthe Sequenom iPLEX genotyping system in a hospital-based cohort with 419 HCC patients treated with TACE,and their associations with HCC overall survival were evaluated by Cox proportional hazard regression analysisunder three genetic models (additive, dominant and recessive). Although we did not find any significant resultsin total analysis (all p>0.05), our stratified data showed that SNP rs9912300 in ACLY gene was significantlyassociated with overall survival of HCC patients with lower AFP level and SNP rs11871275 in ACACA gene wassignificantly associated with overall survival of HCC patients with higher AFP level. We further identified thesignificant interactions between AFP level and SNP rs9912300 or rs11871275 in the joint analysis. Conclusively,our data suggest that genetic variations in genes of DNL pathway may be a potential biomarker for predictingclinical outcome of HCC patients treated with TACE.