The purpose of the article is to study the role of humans in cyber-physical systems and to develop a methodology for assessing the reliability of human-machine interaction and searching for ergonomic reserves to improve the efficiency of cyber-physical systems. The increasing role of a human in cyber-physical systems and the need for special attention to the problems of ergonomics and problems of taking into account the human factor are shown. The need for a human-system approach to the design and operation of cyber-physical systems is proven. A list of indicators of reliability and efficiency of cyber-physical systems is given. The possibility of using a human-machine interaction model built on the principles of “functional networks of Professor A.I. Gubinsky” is demonstrated for ensure the efficiency and ergonomics of cyber-physical systems. The principles of controlled functional networks for managing human-machine interaction in cyber-physical systems are described.