Here, we performed an in vivo proof-of-principle study to assess the benefits of Stk25-targeting antisense oligonucleotides (ASOs), which were either designed to be hepatocyte-specific or broadly distributed to peripheral organs, in blocking the initiation and progression of MASH-related HCC in mice, when administered at different phases of the disease trajectory. The gene discussed is STK25; the disease is hepatocellular carcinoma.