Increasing evidence indicates that activation of oncogenic pathways contributes to an unfavourable tumour immune microenvironment (TIME), ultimately resulting in resistance to immunotherapy. Here, we aim to identify a critical oncogenic pathway involved in an antigen-expressing c-MYC-lucOSOE/Tp53KO HCC mouse model that simulates immune response against tumour-associated antigens in human HCC. To investigate the intrinsic oncogenic pathway enriched in tumours exhibiting immune evasion, tumour tissues were harvested from c-MYC-lucOE/Tp53KO mice and immune-escaped c-MYC-lucOSOE/Tp53KO mice for DIA proteomics.