Autonomous machines are complex systems that are able to perform independent decision-making and to operate without operator’s continuous activities. Increasing autonomy and system complexity create new challenges to safety engineering. In this article, we introduce and discuss about a safety engineering approach that is being developed in VTT for autonomous work-machine applications in close collaboration with machine manufacturers and system suppliers. The main motivation has been to support the early development phases of novel automation solutions and system operating concepts. The system approach focuses on system-level safety issues arising from the shift from manual mobile machines to autonomous machinery systems. It utilizes elements from system safety engineering methods and the latest safety standards for autonomous machinery, as well as the goal-based safety case approach to support the management of safety goals and requirements. The approach and methods are being applied to identify and analyze autonomy related safety risks in several industrial cases.