Curative therapies are not available to greater than 80% of the patient population with hepatocellular carcinoma (HCC). There is a well-recognized need for novel methods that can intricately balance (1) treatment of the disease extent with (2) preservation of liver function and minimizing risk of recurrence and metastasis. Thermoemboliza- tion provides a novel conceptual platform for minimally invasive interventions in which an acid chloride reagent is delivered through an endovascular route via transarterial catheter. The reagent is dissolved in an inert oily solvent and sandwiched between two aliquots of the inert solvent at the leading and trailing edges. Hydrolysis of the acid chloride within the target tissue simultaneously releases the parent acid and an equivalent of hy- drochloric acid. The localized release of acid combined with disruption of the blood supply as well as the heat energy from the exothermic reaction synergistically causes tumor cell death. Current challenges in translating this exciting therapy to patients are a lack of characterization of the mechanisms for a controlled delivery. Project efforts focus on integrating imaging measurements with mathematical model developments to provide key insight in developing this novel thermoembolization treatment approach. The use of high-fidelity predictive models will characterize fundamental mass, thermal, and chemical transport processes needed for control of an effective thermoembolization delivery without unwanted tissue damage. A highly interdisciplinary team with expertise in imaging physics, mathematical modeling, interventional radiology, veterinary pathology, and biochemistry has been assembled to accomplish this goal.