Hepatocellular carcinoma (HCC) is the most common form of liver cancer, originating from liver cells known as hepatocytes. At the molecular level, HCC is driven by transcription factors which are able to reprogram metabolism to support tumorigenesis that are still poorly understood. The Yes-associated protein (Yap) is the nuclear effector of the Hippo pathway, responsible in regulating organ size control and metabolism. Metabolic reprogramming has recently emerged as a fundamental hallmark of cancer. The aim of this study was to determine the role that Yap plays in regulating lipid metabolism in liver cancer. We took advantage of a larval zebrafish model in which a hyperactivated form of Yap is specifically expressed in hepatocytes (lf:YapS87A; lf:NLS-mcherry). We found that the expression of Yap was sufficient to stimulate de novo lipogenesis (DNL) and induce lipid droplet formation in hepatocytes (steatosis). Transcriptomic analyses of the liver tissue revealed that Yap caused an increase in the expression of Sterol regulatory-element binding proteins (SREBP) target genes responsible for DNL. Given that the maturation of SREBP is dependent on the mTOR pathway, we examined the effect of rapamycin treatment. We found that the inhibition of mTOR by rapamycin suppressed Yap driven DNL and hyperplasia. We also demonstrated that the Yap target gene serum/glucocorticoid regulated kinase 1 (SGK1) was required for Yap to induce mTOR-dependent hyperplasia. To determine whether the DNL stimulation was required for Yap-dependent oncogenic growth, we targeted two critical enzymes in DNL, namely FAS and SCD. We observed that both genetic and chemical perturbations of DNL suppressed Yap-dependent hyperplasia, whilst having no effect on normal liver. Together, these findings suggest that oncogenic Yap-driven growth is conditionally dependent upon the SGK1/mTOR/SREBP-mediated stimulation of DNL. Â Consequently, these studies provide a rationale for examining the clinical efficacy of DNL inhibitors to combat liver cancer.