Activated hepatic stellate cells/myofibroblasts induced by TGF-β within the hepatic microenvironment are crucial determinants for cell growth and liver metastasis of colorectal cancer. Notably, TGF-β receptor II serves as the initiator of the received signal, and its membrane localization, internalization, degradation, and trafficking play a decisive role in determining the duration and intensity of TGF-β/SMAD signaling. This study aimed to identify the proteins that interact with TGF-β receptor II and clarify the underlying mechanisms of myofibroblastic activation of HSCs.