Considering that recurrence is a major cause of HCC-related deaths and that the α7-nAChR is a modulator of recurrence, we posit that based on our findings, the α7-nAChR, by interacting with ROCK1 and RhoA, facilitates the loss of HCC cell–cell or cell–membrane adhesion, thereby increasing their motility and invasiveness via activation of MMP2 and MMP9 activities, giving rise to HCC vascular penetration and survival in the circulation, subsequently enhancing the migration of HCC cells into new tissues, and forming distant tumor colonization. Here, MMP2 is linked to hepatocellular carcinoma.