Assessments of ecological integrity have become commonplace for biological conservation, but their role for public health analysis remains largely unexplored. We tested the prediction that the ecological integrity of streams would provide an indicator of human cancer mortality rates in West Virginia, USA. We characterized ecological integrity using an index of benthic macroinvertebrate community structure (West Virginia Stream Condition Index, SCI) and quantified human cancer mortality rates using county-level data from the Centers for Disease Control and Prevention. Regression and spatial analyses revealed significant associations between ecological integrity and public health. SCI was negatively related to age-adjusted total cancer mortality per 100,000 people. Respiratory, digestive, urinary, and breast cancer rates increased with ecological disintegrity, but genital and oral cancer rates did not. Smoking, poverty, and urbanization were significantly related to total cancer mortality, but did not explain the observed relationships between ecological integrity and cancer. Coal mining was significantly associated with ecological disintegrity and higher cancer mortality. Spatial analyses also revealed cancer clusters that corresponded to areas of high coal mining intensity. Our results demonstrated significant relationships between ecological integrity and human cancer mortality in West Virginia, and suggested important effects of coal mining on ecological communities and public health. Assessments of ecological integrity therefore may contribute not only to monitoring goals for aquatic life, but also may provide valuable insights for human health and safety.