No biomarkers related to the PD-1/PD-L1 axis are currently available for helping clinical practice, but the relevance of the PD-1/PD-L1 axis in the pathogenesis of MASLD suggests the intriguing possibility of using these molecules as biomarkers for the early identification of disease and for assessing the risk of progression, especially in the onset of HCC development in MASLD. This evidence concerns the gene PDCD1 and hepatocellular carcinoma.