World-wide, hepatocellular carcinoma (HCC) is among the most common cancers and frequently overexpresses the c-Myc (Myc) oncoprotein. Using a mouse model of Myc-induced HCC in which Myc can be rapidly induced, silenced and re-espressed, we have studied the metabolic, biochemical, and molecular changes accompanying HCC progression, regression, and recurrence. These involved altered rates of pyruvate and fatty acid β-oxidation and the likely re-directing of glutamine into biosynthetic rather than energy-generating pathways. Initial tumors also showed reduced mitochondrial mass and differential contributions of electron transport chain complexes I and II to respiration. The uncoupling of complex II's electron transport function from its succinate dehydrogenase activity also suggested a mechanism by which Myc generates reactive oxygen species. RNA sequence studies revealed an orderly progression of transcriptional changes involving pathways pertinent to DNA damage repair, cell cycle progression, insulin-like growth factor signaling, innate immunity, and further metabolic re-programming. Only a subset of functions deregulated in initial tumors was similarly deregulated in recurrent tumors thereby indicating that the latter can "normalize" some behaviors to suit their needs. An interactive software tool was developed to allow continued analyses of these and other transcriptional profiles (see: https://prochownik.pitt.edu/hcc. Collectively, these studies define the metabolic, biochemical, and molecular events accompanying HCC evolution, regression, and recurrence in the absence of any potentially confounding therapies. We are continuing to refine this model and are currently exploring how various dietary alterations such as long-and medium-chain high fat diets impact the initiation and progression of these tumors and the associated metabolic re-wiring that accompanies tumorigenesis.