Cells are in complicated mechanical and physical microenvironment in vivo. The former mainly includes flow shear, tension, compression or torsion, and the latter covers stiffness and topography of extracellular matrix, spatial location, volume constraint or osmotic pressure, featured with various types, patterns, and parameters of mechanical or physical loading. Cell biomechanics mainly focuses on the alteration of mechanical properties of cells and the mechanical remodeling of subcellular components, the cell development, growth, proliferation, differentiation, and apoptosis under distinct mechanical stimuli, and the cellular sensation, transmission, transduction, and responses to external forces. This review summarized the major progresses in cell biomechanics in 2021, including studies on cardiomyocytes, endothelial cells, osteoblasts, immune cells, cancer cells and stem cells, as well as the related new techniques.