On the basis of the hydrological and meteorological data in the Aksu River Basin during 1960-2010, the multi-scale characteristics of runoff variability were analyzed using the ensemble empirical mode decomposition method (EEMD), and the aim is to investigate the oscillation mode structure characteristics of runoff change and its response to climate fluctuation at different time scales. Results indicated that in the past 50 years, the overall runoff of Aksu River in northwestern China has exhibited a significant non-linear upward trend, and its changes obviously manifested quasi-3 and quasi-6-7 years at inter-annual scale and showed quasi-13 and quasi-25 years at inter-decadal scale. Variance contribution rates of each component showed that the inter-annual change held a dominant position in the overall runoff change, and the inter-decadal change also played an important role in the overall runoff change for the Aksu River. The reconstructed inter-annual variation could describe the fluctuation state of original runoff during the study period; the reconstructed inter-decadal variability effectively revealed that the runoff for the Aksu River changed over the years, namely the state of abundance and low water period appear alternately. In addition, we found that runoff has a positive correlation to precipitation, temperature and potential evaporation (PET) at the inter-annual scale, but not significant in statistics. The runoff has a significant positive correlation to precipitation and temperature whereas a negative correlation to PET at the inter-decadal scale, furthermore, they are more significant and relevant at inter-decadal scale, indicating that the inter-decadal scale is more suitable for investigating the responses of runoff dynamics to climate fluctuation. Meanwhile, the results also suggested that EEMD is an effective method to distinguish the non-linear trend from multi-scale variability of non-linear and non-stationary signal and can be helpful to deepen the understanding of the multi-scale characteristics for runoff in arid area of the northwestern China.