Multilayer perceptron is composed of massive distributed neural processors interconnected. The nonlinear dynamic components in these processors expand the input data into a linear combination of synapses. However, the nonlinear mapping ability of original multilayer perceptron is limited when processing high complexity information. The introduction of more powerful nonlinear components (e.g., S-box) to multilayer perceptron can not only reinforce its information processing ability, but also enhance the overall security. Therefore, we combine the methods of cryptography and information theory to design a low-power chaotic S-box (LPC S-box) with entropy coding in the hidden layer to make the multilayer perceptron process information more efficiently and safely. In the performance test, our S-box architecture has good properties, which can effectively resist main known attacks (e.g., Berlekamp Massey-attack and Ronjom–Helleseth attack). This interdisciplinary work can attract more attention from academia and industry to the security of multilayer perceptron.