Network toxicology that is an important branch of the network pharmacology emerges on the basis of network biology. It refers to study on the toxicological features of a constructed network model which is used to analyze toxic substances and their interaction and regulation in biological systems, particularly investigate the toxic effects of drugs and/or compatibility of medicines on body, and clarify the mechanism of toxicity. Network toxicology currently develops rapidly in safety prediction of Chinese materia medica(CMM). The application of network toxicology to safety and toxicology study on CMM is extremely beneficial to identify the toxic components and potential incompatibility of CMM. Since CMM is a complex system with multi-components, multi-targets, and multi-interactions, the network toxicology in safety prediction of CMM faces three great challenges, including integration studies of bioinformatics, innovation of methods, and tools and risk assessment in future development of the network toxicology in CMM research. In this paper, relevant database, approaches and tools that network toxicology utilized in the safety study of CMM were carefully reviewed. Based on the progress made, the scientific development and modernization of CMM will be greatly enhanced. Network toxicology that is an important branch of the network pharmacology emerges on the basis of network biology. It refers to study on the toxicological features of a constructed network model which is used to analyze toxic substances and their interaction and regulation in biological systems, the toxic effects of drugs and / or compatibility of medicines on body, and clarify the mechanism of toxicity. Network toxicology currently develops rapidly in safety prediction of Chinese materia medica (CMM). The application of network toxicology to safety and toxicology study on CMM is extremely beneficial to identify the toxic components and potential incompatibility of CMM. Since CMM is a complex system with multi-components, multi-targets, and multi-interactions, the network toxicology in safety prediction of CMM faces three great challenges, including integration studies of bioinformatics, innovation of methods, and tools and risk assessment in future development o f the network toxicology in CMM research. In this paper, relevant database, approaches and tools that network toxicology utilized in the safety study of CMM were carefully reviewed. Based on the progress made, the scientific development and modernization of CMM will be greatly enhanced.