Modulation of Tspan5 in HCC cells has shown that Tspan5 promotes the cell migration and tumour metastasis of HCC by increasing the enzymatic maturation of ADAM10, activating Notch signalling via increasing the cleavage of Notch S3 site catalyzed by γ‐secretase, and enhancing Notch‐dependent EMT and actin skeleton rearrangement of HCC cells. This evidence concerns the gene TSPAN5 and neoplasm.