Mining activities have increased the potential risks of metal pollution to the groundwater resources in arid areas across the globe. Therefore, this study aimed to examine the health risk associated with nickel (Ni) in the groundwater sources of a mining-impacted area, South Khorasan, Eastern Iran. A total of 110 stations were included in the study, comprising 62 wells, 40 qanats, and 8 springs in summer, 2020. Initially, the collected samples were tested for temperature, pH, and electrical conductivity (EC). Subsequently, the samples were filtered and treated with nitric acid (HNO3) to measure the concentration of Ni using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Hazard quotient (HQ) and non-carcinogenic risk assessments were employed to evaluate the potential risks of Ni to the inhabitants. The findings revealed that the concentration of Ni ranged from 0.02 to 132.39 μg l−1, and only two stations exhibited Ni concentrations above the WHO standards (20 μg l−1). The results demonstrated that 98.21% of the sampled locations had HQ values below one, indicating negligible risk, while 1.78% of the stations exhibited HQ values of one or higher, representing a high non-carcinogenic risk for water consumers. Overall, the concentration of nickel in the groundwater of South Khorasan exceeded the World Health Organization (WHO) limit solely in the Halvan station, posing a non-carcinogenic risk for the residents in that area, and therefore, additional efforts should be made to provide healthier groundwater to consumers in this region.