Objective To establish the finite element model of knee joint and investigate changes of stress and strain in normal and cartilage sclerosis cases, so as to provide reference for clinical treatment of the knee osteoarthritis. Methods CT scanning images of normal knee joint were used to establish the 3D finite model using Mimics and ANSYS software. Loadings of 350 N pressures were applied on the model of normal knee joint and knee joint with cartilage sclerosis, respectively. The related material parameters of cartilage before and after sclerosis were set, and the Von Mises stress and strain changes of the knee joint were then analyzed. Results In case of cartilage sclerosis, the function of shock absorption and load transfer in articular cartilage basically disappeared. The stress and strain on the femur changed with uneven distribution, showing more obviously than those on the inner and outer condyle, and the overall stresses were increased obviously. The largest stress and strain occurred on the meniscus. Conclusions The long-term cartilage destruction will affect nutrient metabolism of articular cartilage and cause the deterioration of osteoarthritis diseases. This study can preferably explain the pathogenic mechanism of osteoarthritis, and also provide relevant data for establishing parametric study system.