Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), represent growing global health burdens, with a significant subset advancing to hepatocellular carcinoma (HCC). While recent multi-omics approaches have identified key molecular drivers in this progression, comprehensive mutational analyses, particularly of insulin-like growth factor 1 (IGF1), remain underexplored. This study addresses this gap through an integrative pan-cancer bioinformatics analysis of IGF1 mutations and their clinical relevance. Using the TCGA Pan-Cancer dataset (N=10,535), we characterized the IGF1 mutational landscape, revealing distinct mutation profiles across cancer types, with notable prevalence in HCC. IGF1 expression significantly correlated with advanced tumor stage (T3/T4 vs. T1/T2, p<0.0001) and demonstrated strong associations with immune cell infiltration patterns, particularly macrophages and T-cells. Furthermore, IGF1 expression showed significant correlations with tumor mutational burden (TMB), microsatellite instability (MSI), and immune checkpoint molecules, suggesting its role in modulating the tumor immune microenvironment. Copy number variation analysis revealed frequent IGF1 amplifications in tumor versus normal tissues across multiple cancers. These findings position IGF1 not only as a progression biomarker in MASLD-MASH-HCC continuum but also as a potential immunomodulatory target. This study provides a comprehensive mutation-centric framework for understanding IGF1’s role in liver disease progression and offers insights for developing precision medicine strategies targeting IGF1 signaling in HCC.