This paper presents an application of design of experiments techniques to determine the optimized parameters of artificial neural network (ANN), which are used to estimate force from Electromyogram (sEMG) signals. The accuracy of ANN model is highly dependent on the network parameters settings. There are plenty of algorithms that are used to obtain the optimal ANN setting. However, to the best of our knowledge they did not use regression analysis to model the effect of each parameter as well as present the percent contribution and significance level of the ANN parameters for force estimation. In this paper, sEMG experimental data are collected and the ANN parameters based on an orthogonal array design table are regulated to train the ANN. Taguchi help us to find the optimal parameters settings. Next, analysis of variance (ANOVA) technique is used to obtain significance level as well as contribution percentage of each parameter to optimize ANN’s modeling in human force estimation. The results indicated that design of experiments is a promising solution to estimate the human force from sEMG signals.