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This article looks into the mapping of Mark Twain’s writing from humanism to post – humanism with special attention to the influence of his Chinese – related writings on the shift from humanism to post – humanism. By having a comprehensive analysis of Twain’s non – fictional and fictional works such as his journalistic and political articles, “The Fable of the Yellow Terror” and “Three Thousand Years among Microbes”, I argue that Twain’s anguishing works toward the end of his life cannot be neatly defined by the preoccupation of existential pessimism or as the “great dark writing” that overlook his consistent concern with human nature. Instead, reflecting upon the place of human beings in the universe, Twain’s later writing manifests a intricate state of post – humanism that challenges the anthropocentrism which puts human’s rights and interests as priority above other livings objects. In the mapping process of his pos t – humanism, his earlier encounter with Chinese immigrants as the victim of racism and his involvement into the movement of anti – imperialism as expressed in his outcry against the presences of imperialism in China as well as his sympathy and support for the Boxer Movement, have enabled Twain to wrestle with the dilemma of racism, nationalism and any other types of centrism. His bitter contemplation over international politics, racial equality and cultural differences is further developed into an audacious and courageous plan of seeking a way out to reconsider human race’s relationship with other living objects ranging from living animals to microbes in a post – humanistic context by the end of his career.