In summary, this study revealed that abnormal expression of ASPM plays a pivotal role in the progression of HCC through interacting with Dvl2, physically preventing the formation of Dvl2 and LC3II protein complex, and augmenting the Wnt–ASPM–Dvl‐2–β‐catenin signaling axis, which not only sheds a new light on HCC progression but also provides a potential target for HCC treatment. Here, ASPM is linked to hepatocellular carcinoma.