By employing a comprehensive multi‐omics approach, this study provided the most comprehensive single‐cell profiling of the ecosystem in post‐HAIC HCC, not only presenting a high‐resolution description of cellular diversity at the spatial and temporal levels, but also delineating the molecular underpinnings of combining HAIC with PD‐1 blockade. This evidence concerns the gene PDCD1 and hepatocellular carcinoma.