Soil dissolved organic matter (DOM) is crucial to atmospheric, terrestrial and aquatic environments as well as human life. Here, by characterizing DOM from 89 grassland soils throughout China, we reveal the spatial association between DOM geochemistry in the dry season vs annual ecosystem exchange and cancer cases. The humic-like and high molecular weight (3.4-25 kDa) fractions with lower biodegradability, decline from the northern to the southern regions of China, and are correlated with lower soil respiration and net ecosystem productivity at the continental scale. The <1.2 kDa and proteinaceous fractions could serve as a geographical indicator of nasopharyngeal cancer incidence and mortality, while the 3.4-25 kDa and humified fractions are potentially associated with pancreatic cancer cases (P < 0.05). Our findings highlight that exploiting the environmental functions of soil DOM and mitigating the negative impacts are necessary, and require actions tailored to local soil DOM conditions.© 2024. The Author(s).