After screening and intersecting samples from two different populations, we identified eight plasma protein–protein pairs (ERBIN/LAT2, ICA1/IRAK1, ICA1/YTHDF3, ITGB1BP2/LAT2, LAT2/SPRY2, FAP/THBS4, PPP1R9B/TDRKH, and STK24/TDRKH) that were strongly associated with HCC. This evidence concerns the gene SPRY2 and hepatocellular carcinoma.