The tumour microenvironment (TME) is made up of cancer, stromal and immune cells, and is associated with various cancer types. In hepatocellular carcinoma (HCC), the TME landscape has been associated with prognostic outcomes, but there is still more to be investigated. Our work aims to provide further insight into the TME landscape within HCC, and how it contributes to prognostic outcomes. Thirty-two treatment naïve patients with HCC undergoing curative resection at a single tertiary institution were identified. Tissue microarrays (TMAs) were created from regions of interest within the tumour, invasive margin, and peri-tumour. An imaging mass cytometry panel consisting of forty immune markers was optimised and stained on the TMA. Spatial analyses were undertaken to interrogate differences between regions and clinical parameters. Our high-dimensional panel allowed the identification of a wide range of cancer, stromal and immune cell subsets. Using principal component analysis and spare partial least squares-discriminant analysis we revealed differences in subset density and interactions between cell subsets in each region. These in turn were associated with various patient aetiologies, including microvascular invasion and viral-associated HCC. Our analyses provide insight on how various regions contribute to clinical outcomes.