In metastatic hepatocellular carcinoma (HCC), mass spectrometry protein analysis of HCC‐derived sEV (HCC‐sEV) identified an upregulation of nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in maintaining cellular nicotinamide adenine dinucleotide (NAD+) levels. Here, NAMPT is linked to hepatocellular carcinoma.