Fructose metabolism utilizes a distinct set of transporters and enzymes and is limited to the liver, kidney and small intestines. Key to the ability to break down fructose is the enzyme ketohexokinase (KHK), that phosphorylates fructose to fructose-1-phosphate (F1P). In this study, we demonstrate that fructose metabolism is downregulated in a mouse model of hepatocellular carcinoma (HCC). Based on this novel observation, we use 13C nuclear magnetic resonance (NMR) to quantify altered hepatic fructose metabolism. We demonstrate significantly decreased F1P production in HCC, providing justification for developing non-invasive methods to detect fructose metabolism.