To fully understand the role of OPN on the development of NAFL‐derived hepatocellular carcinoma (HCC), we applied a non‐alcoholic steatohepatitis (NASH)‐HCC mouse model on osteopontin‐deficient (Spp1−/−) mice analysing time points of NASH, fibrosis and HCC compared to wild‐type mice. This evidence concerns the gene SPP1 and metabolic dysfunction-associated steatohepatitis.