Plague has caused the death of hundreds of millions of people throughout the human history. Today this disease is again re-emerging and hence is again becoming an increasing threat to human health in several parts of the world. However, impacts of global climate variation (e.g. El Nino and Southern Oscillation [ENSO]) and global warming on plagues are largely unknown. Using cross-spectral analysis and cross-wavelet analysis, we have analyzed the relationship between increase rate of human plague in China during 1871-2003 and the following climate factors (as measured by the Southern Oscillation Index [SOI], Sea Surface Temperature of east Pacific equator [SST] and air Temperature of the Northern Hemisphere [NHT]). We found in the frequency domain that increase rate of human plague was closely associated with SOI and SST. Cross-spectral analysis reveals that significant coherencies between increase rate of human plague and ENSO were found over short periods (2-3 years), medium periods (6-7 years) and long periods (11-12 years, 30-40 years). Cross-wavelet analysis reveals that increase rate of human plague oscillates in phase with SOI, but in anti-phase with SST over periods of 2-4 years and approximately 8 years (6-10 years). These results indicate that ENSO-driven climate variation may be important for occurrences of human plague in China. However, there is a need for a further analysis of the underlying mechanism between human plague in China and ENSO.