In general, we revealed a new effect of GRAMD4 on the motility and metastasis of HCC cells, revealing how GRAMD4‐TAK1 interaction impaired the stability of TAK1 to decrease the activation of MAPK and NF‐κB signalling, which suppressed the motility and lung metastasis of HCC cells. Here, NFKB1 is linked to hepatocellular carcinoma.