Liver cancer is the sixth most common cancer and the third leading cause of cancer-related mortality worldwide. Obesity is beginning to overtake hepatitis viruses as the major cause of liver cancer in the Western world, contributing up to 50% of cases. Obesity drives liver cancer development and progression through chronic inflammation, hepatic lipid accumulation, immune dysfunction, and therapeutic resistance. Obesity therefore represents a major barrier to effective treatment and improved clinical outcomes in liver cancer patients. This presentation will highlight new research investigating the anti-tumour potential of targeting obesity using the mitochondrial uncoupler molecule, BAM15. BAM15 works by increasing nutrient oxidation inside mitochondria and results in fat-specific weight loss in obese mice. In a diet-induced obese mouse model of liver cancer, BAM15 significantly enhanced the anti-tumour effects (>70% reduction in tumour growth) of frontline liver cancer therapies including sorafenib. In contrast, the monotherapies did not significantly alter tumour growth. Investigation of the liver tumours showed the drug combination of BAM15 with sorafenib led to increased infiltration of immune cells, including T-cells. Collectively, these findings support further exploration of BAM15 as a novel therapeutic to enhance the effectiveness of cancer therapies for the treatment of liver cancer and other obesity-related cancers.