The Internet-of-Things (IoT) has enabled Industry 4.0 as a new manufacturing paradigm. The envisioned future of Industry 4.0 and Smart Factories is to be highly configurable and composed mainly of the ‘Things’ that are expected to come with some, often partial, assurance guarantees. However, many factories are categorised as safety-critical, e.g. due to the use of heavy machinery or hazardous substances. As such, some of the guarantees provided by the ‘Things’, e.g. related to performance and availability, are deemed as necessary in order to ensure the safety of the manufacturing processes and the resulting products. In this paper, we explore key safety challenges posed by Industry 4.0 and identify the characteristics that its safety assurance should exhibit. We pro-pose a modular safety assurance model by combination of the different actor responsibilities, e.g. system integrators, cloud service providers and “Things” sup-pliers. Besides the desirable modularity of such a safety assurance approach, our model provides a basis for cooperative, on-demand and continuous reasoning in order to address the reconfigurable nature of Industry 4.0 architectures and ser-vices. We illustrate our approach based on a smart factory use case.