To interrogate the function of KDM6A in liver cancer we applied a powerful mouse model and found that Kdm6a loss in combination with c-myc leads rapidly to liver tumours and further by establishing an endogenous reactivation system for Kdm6a we show that sustained loss of Kdm6a is important for liver tumour maintenance, thereby clearly underscoring the importance of Kdm6a as a tumour suppressor in liver cancer. Here, KDM6A is linked to liver cancer.