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Mushrooms in the basidiomycete family Amanitaceae are very important both economically and ecologically. However, the delimitation of the family is still controversial, in part due to limited taxon sampling and in part because of insufficient gene fragment employed for molecular phylogenetic analyses. Furthermore, species diversity in the family is likely to have been largely underestimated, due to morphological similarity between taxa and phenotypic plasticity. In this study, we examined 1190 collections, including 1008 Chinese and 182 external ones, and performed the first comprehensive phylogenetic analyses of Amanitaceae using multi-locus sequence data. To test the monophyly of the Amanitaceae, a concatenated (nrLSU, rpb1, and rpb2) dataset of 200 taxa of the order Agaricales was analyzed. To infer the phylogeny of Amanitaceae, a concatenated nrLSU, tef1-α, rpb2 and β-tubulin dataset (3010 sequences from ca. 890 samples with 2309 newly generated sequences) was used. In this dataset, 252 sequences from the types of 77 species were provided. Our results indicate that Amanitaceae is a monophyletic group, and consists of five genera, namely Amanita, Catatrama, Limacella, Limacellopsis and Myxoderma. It is clear that Catatrama is closely related to Limacella, however, the phylogenetic relationships among these genera remain largely unresolved. Amanita contains 95% of the species in the family, and is here divided into three subgenera and eleven sections (subgen. Amanita, containing: sect. Amanita, sect. Amarrendiae, sect. Caesareae and sect. Vaginatae; subgen. Amanitina, containing: sect. Amidella, sect. Arenariae, sect. Phalloideae, sect. Roanokenses, sect. Strobiliformes and sect. Validae; and subgen. Lepidella, containing sect. Lepidella). Subgen. Lepidella occupies the basal position in the genus. One-hundred and sixty-two species of Amanitaceae known from China are treated in this study, including 50 novel species and 112 known taxa. Amanita gleocystidiosa, A. pyriformis, A. atrofusca, A. subjunquillea var. alba and A. areolata are treated as synonyms of A. sychnopyramis f. subannulata, A. orientigemmata, A. umbrinolutea, A. subjunquillea and A. zangii, respectively. 26 extralimital taxa including a novel species, namely Catatrama indica, were included in our study to allow us to make comparisons between these and the Chinese taxa. DNA sequence data for all the species of Amanitaceae in China and keys for identification of the species are provided.