Numerous quantitative studies have confirmed that climate change has had an important impact on the traditional agriculture-oriented Chinese society. Most of the related existing studies used temperature, precipitation, droughts and floods as the main variables for analysis and overlooked the impact of only drought disasters on social instability; however, drought is most closely related to famine. Moreover, previous studies lacked information on the contribution of climate-driven droughts in different regions and time scales to the national social instability. To solve this problem, this study conducted a quantitative analysis of the regional drought and national famine indexes during the Han dynasty and explored the influence and contribution of the regional droughts to the national instability, further exploring the root cause of the demise. Conclusion: In the Han dynasty, drought was an important factor for inducing social instability in China, but the regional differences were obvious. Droughts in Henan Province contributed the most to the social instability in China. Although the regional droughts in Henan Province were mainly responsible for the social instability and the demise of the dynasty, the abrupt climate change caused by the droughts was not the fundamental cause of the demise of the Han dynasty. The relationship between climate and famine is influenced by several regional factors; thus, we should comprehensively study the ancient human-land system. When the relationship between people and the land in historical periods is studied, the data from different regions should first be divided and then analyzed independently, to fully consider the regional differences.