In this study, we treated [HBx, Src, RPIA, p53−/−] transgenic zebrafish which develop HCC at 5 months of age, with WNK1–SPAK/OSR1 axis inhibitors combined with oligo-fucoidan to further improve the efficacy of WNK1–OSR1 axis inhibitors combined with oligo-fucoidan to protect the normal cells. The gene discussed is RPIA; the disease is hepatocellular carcinoma.