Climate change is the principal driving factor for the changes of runoff in the rivers. Analyzing the climate change in the basin and the hydrological response of runoff is of great significance to the effective adaption of global warming. Using Princeton Global Forcing Database and the monitored runoff data of eight hydrological stations in the mainstream of Lancang-Mekong River Basin, variations of temperature and precipitation in different regions, and hydrological responses of runoff to climate change in different hydrological phases during 1960-2012 were investigated. Results show that the variation of annual temperature presented a significant rising trends during 1960-2012 for all of the eight regions in the basin exceeding >0.2 ℃/10a. Meanwhile, annual precipitation in the region of Jiuzhou-Yunjinghong decreased while the rest of the seven regions increased to various degrees. At seasonal scale, spring precipitation increased for all of the eight regions while winter precipitation decreased for most regions. Abrupt changes in annual runoff coefficient series mainly occurred in the 1960s. The interaction between precipitation and runoff varied from region to region and phase to phase. Under the same condition of precipitation, runoff yield after 2000 was much higher than that in the previous phases for the region of Luang Prabang- Mukdahan; however, runoff yield in the later phase was mostly lower than that in the first phase for the regions of Jiuzhou-Yunjinghong and Chiang Saen- Luang Prabang.