The soil pollution status, levels of exposure, and potential ecological and health risks to workers and residents by potentially harmful elements (PHEs) in the Angouran mining area (Iran), the biggest Zn–Pb mine in the Middle East, were studied. To this aim, topsoil (0–5 cm) samples (n = 63) from different land-uses were analyzed for their total PHEs concentrations. Mine worker's blood analysis and in vitro digestion extractions were applied in conjunction with human health risk assessment (HHRA) to assess the potential health impacts by exposure to PHEs. The maximum PHEs total concentrations were found in the soils near the waste rock dumps. HHRA indicated that ingestion of soils may induce a non-carcinogenic risk due to As and Pb (for both age groups of children and adults), while dermal contact for children may induce the same type of risk due to Cd, and Pb. The carcinogenic risks (CRs) of As, Cd, Cr, and Ni through ingestion route were above the acceptable value of 1 × 10−4, and children may face greater health risks. The average blood Zn, Pb, and Cd levels in the mine workers largely exceeded the safe concentration for adults, while 30% of the workers were tested positive for As in blood. In vitro digestion extractions indicated that the highest bioaccessible contents of As, Cd, Pb, Ni and Zn were found for the industrial-residential and mine soils in the area, while those of Cr and Cu were observed in the agricultural use soils. This study illustrates that a combination of techniques, including geochemical analysis, in vitro bioaccessibility extractions, HHRA, and blood analysis, is a workable integrated approach for evaluating pollution and health risks in mining districts.
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