The pathogenesis of hepatocellular carcinoma (HCC) strongly relates to inflammation, with chronic up-regulation of pro-inflammatory mediators standing as a potential unifying mechanism that underscores the origin and progression of HCC independent of aetiology. Activation of the diverse pro-inflammatory mediators either within the tumour or its microenvironment is part of an active cross-talk between the progressive HCC and the host, which is known to influence clinical outcomes including recurrence after radical treatments and long-term survival. A number of clinical biomarkers to measure the severity of cancer-related inflammation are now available, most of which emerge from routine blood parameters including neutrophil, lymphocyte, platelet counts, as well as albuminaemia and C-reactive protein levels. In this review, we summarise the body of evidence supporting the biologic qualification of inflammation-based scores in HCC and review their potential in facilitating the prognostic assessment and treatment allocation in the individual patient. We also discuss the evidence to suggest modulation of tumour-promoting inflammation may act as a source of novel therapeutic strategies in liver cancer. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.