The musculoskeletal model plays an important role in the investigation of human lower limb diseases.Although different methods are used for musculoskeletal models, the prediction of the tibiofemoral and muscle forces still needs more improvements. This paper introduces a model for the lower limb; 3-DOF hip, 1-DOF knee, and 3-DOF ankle. The model estimates the tibiofemoral and muscle forces based on static optimization. The shank and the foot are considered as one element to avoid the high-cost computation of the traditional inverse dynamic method. The direction of the tibiofemoral force is estimated based on the analytical method to tune the weight factors o the predicted force. Two subjects (A and B) performed walking at 1m/s for about 5 gait cycle with recording the kinematics, ground reaction force (GRF), and foot center of pressure (CoP) and electromyographic (EMG) signals. A static optimization technique was performed to predict the tibiofemoral and 6 lower limb muscles forces based on the 2 nd -Newton law in three-dimensional (3D). Muscles moment arms were verified by compared to measured data in the literature. The validity of the model was guaranteed by testing the model on a subject of total knee replacement (TKR) and compared the predicted tibiofemoral force with the measured one. The predicted tibiofemoral forces had the root mean square error (RMSE) of 0.19, 0.56, and 0.43 BW for TKR subject, subject A and subject B, respectively. The predicted muscles force was validated by comparing it to EMG signals. The analysis and the validation of the model showed that it could be used for different activities like walking and running and assessment rehabilitation devices such as knee brace.INDEX TERMS Musculoskeletal model of the lower limb, tibiofemoral force prediction, muscle force estimation, static optimization.