Elevated contents of mercury (Hg) and nickel (Ni) in soils and foodstuffs can threaten human health. As contents of these metals in soil, water, and food vary from place to place, the associated risks will also be different in various parts of a region and it should be considered for environmental decision-making and human health management. In this study, the authors mapped the variation of human health risks related to Ni and Hg in soil, water, and foodstuffs across an entire region, in province of Hamedan western Iran as an example case. Risks were calculated using the methods proposed by USEPA. The risk maps showed that total non-cancer relative risks of Ni and Hg were much >1 (critical level). Risk of Ni in Razan and Kaboudarahang was higher than other counties. For some areas, relative non-cancer risks associated with exposure to Hg were estimated up to 7 and 11 in children and adults respectively. Consumption of plant foods particularly wheat was found to be the major route of human exposure to Ni and Hg. Soil ingestion was found to be another important route of human exposure to these metals.