Lecture : Liver cancer is a dreadful disease with limited therapeutic options. Genomic heterogeneity and late-stage diagnosis complicate precision medicine and preventive therapies in liver cancer. However, proper preclinical models for studying human liver cancers are largely missing. We recently established human-liver cancer-derived cell lines propagated in 2D-cultures and genetically engineered reprogrammed hepatocyte organoids ( hiHeps ) modeling liver cancer initiation. We built 66 primary liver cancer cell lines ( LIMORE ) , which provides a rich resource reflecting genomic heterogeneity to study driver mutations and drug responses for precision medicine. Recently, engineered hiHep organoids was established as a tractable system for modelling liver cancer initiation and identifying potential preventive therapies.