The controllability of hardness and its control method, the corresponding direction of differentiation of mesenchymal stem cells (MSCs) regulated by different hardness, and the role of integrin in the signaling pathway through which hardness regulates MSCs differentiation were briefly described in this paper. Among them, the role of integrin in the signaling pathway of hardness regulation of MSCs differentiation was highlighted. Signal pathways in which hardness regulates MSCs differentiation include Rho/ROCK signal pathway, integrin/FAK signal pathway, ERK signal pathway, JNK signal pathway, Wnt-catenin signal pathway and PI3K/Akt signal pathway, etc. Integrin, as a transmembrane heterodimer glycoprotein, participates in part of the signal pathway to transmit mechanical signals to MSCs. Different integrin families participate in different signaling pathways to regulate the differentiation of MSCs in different directions, and there are certain mutual influences among these signaling pathways. The research findings provide a theoretical basis for the application of tissue repair, organ reconstruction and regenerative medicine.