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This paper examines spatio-temporal characteristics of an oasis economy and its relationship with water and mineral resources in the Tarim River Basin from 1965 to 2005. A spatial autocorrelation model, the center of gravity model, and index system of the regional central city are used to probe the evolution laws of spatial structure of oasis economy. The study finds that: 1) The economic centre of gravity, whose variation track during this period follows linear rate law, was moving from headstream to middle reaches of the Tarim River. 2) Positive spatial autocorrelation which showed a waving and ascending trend of regional economy was significant and the neighbor effect of regional economic growth was strengthened continuously. 3) The regional economic centre was located in Hotan City before 1980, moved to Aksu City during the 1980s and to Korla City after 1990. We conclude that above all, during the recent four decades the evolution of the oasis economy in this region has gone through three stages: a traditional agriculture stage (before 1980), oasis agriculture and agricultural product processing stage (1980)(1981)(1982)(1983)(1984)(1985)(1986)(1987)(1988)(1989)(1990) and oasis energy industry stage (after 1990). Furthermore, the dependence degree of the oasis economy on natural resources in different stages are studied by using dominance index, regression model, and grey relation method, which shows that an oasis economy highly depends on water resources in the oasis agriculture and agricultural product processing stage while it depends more on mineral resources such as oil and natural gas during the oasis energy industry stage.