In this study, the 54-year (1950 to 2003) monthly runoff series from February, April,August, and November, as well as the annual runoff series, measured at both Huayuankou and Lijin hydrological stations were chosen as representative data, and the continuous wavelet transform (CWT) was applied to analyze the impacts of human activities on the runoff regime of the middle and lower Yellow River. A point of change in 1970 was first determined, and the observed series before 1970 were considered natural runoff while those after 1970 were restored according to linear trends. Then, the CWT was applied to both the observed and restored runoff series to reveal their variations at multi-temporal scales, including the five temporal ranges of 1-4,6-8, 9-12, 16-22, and 22-30 years, and the trend at the temporal scale of 54 years. These analysis results are compared and discussed in detail. In conclusion, because of the impacts of human activities, there have been significant changes in the runoff regime in the middle and lower Yellow River since 1970. The decaying tendency of annual runoff has become more pronounced, and the inner-annual distribution of runoff has changed, but human activities have had little impact on the periodic characteristics of runoff.