Hepatocellular carcinoma (HCC) is a common malignant tumor disease in China. In recent years, more and more attention has been paid to the influence of microenvironment on cancer tissue. Extracellular matrix (ECM), as an important microenvironment component of HCC tissue, plays an important role in tumor occurrence and development, involving tumor growth, apoptosis, drug resistance, invasion, metastasis and so on. The fibronectin (FN), laminin (LN), hyaluronic acid (HA), collagen (COL) and matrix stiffness play special roles in the tumorigenesis and progression of HCC. It is precisely because of the special role of each protein component of ECM in HCC, blindly degrading or knocking out any protein component in ECM may probably not be able to achieve the desired therapeutic effect, but accelerate the progress of HCC. Therefore, it is necessary to explore some specific drugs or methods for targeted regulation of ECM components, and purposeful control of ECM remodeling, thus affecting the occurrence and development of HCC. Considering that the microenvironment of HCC is a dynamically changing environment, it is a feasible research direction for exploring the co-action of ECM multi-components on HCC cells by co-culture of HCC cells with multiple ECM protein components instead of a single component to simulate the microenvironment of HCC cells as much as possible.