Thermal ablation (TA) is commonly used to treat early hepatocellular carcinoma (HCC) and liver metastases. However, there is increasing clinical and experimental evidence that TA may sometimes induce more aggressive tumor biology within and outside the liver. We used hyperpolarized 13C MRI to detect increased HCC lactate flux following adjacent normal liver radiofrequency ablation in a rat model. This increased flux correlated with an increase in tumor expression of PFKFB3, a known modulator of glycolysis. PFKFB3 may be a potential therapeutic target and hyperpolarized 13C MRI may be used to track or predict treatment response.