We carried out an epidemiological study to assess the impact of flood on the quality of life (QOL) of residents in the affected areas in China. We used a natural experiment approach, randomly selected 494 adults from 18 villages, which suffered from flooding as a result of embankments collapsing, 473 adults from 16 villages, which suffered from, soaked flood, and 773 adults from 11 villages without flood (control group). We used the Generic QOL Inventory-74 (GQOLI-74), social support scale, and questionnaires to assess the QOL of all study participants. The QOL was significantly poorer in soaked group (58.4) and (especially) in collapsed group (55.1) than in control group (59.5, p<0.001). Adjustment for potential confounding factors did not change the results. The impact of flood on QOL was stronger among farmers, seniors, persons with introvert personality, and residents with adverse life-events, whereas social support and extrovert personalities offset the negative impact of flood on QOL.