Objectives: Few spatial studies on Keshan disease (KD) prevalence and serum selenoprotein P (SELENOP) levels have been reported in the Heilongjiang Province, China. This study aimed to investigate the spatial relationships between KD prevalence, SELENOP levels, and the socio-economic status for the precise prevention and control of KD. Material and Methods: The study was carried out in all the 66 KD endemic counties in the Heilongjiang Province using a non-probability sampling method of a key village survey based on county-wide case-searching. The participants completed a questionnaire and had their serum SELENOP levels measured using enzyme-linked immunosorbent assay. Thematic maps were created, and spatial regression analysis was performed by ordinary least squares using ArcGIS 9.0. Results: Overall, 53 676 residents were surveyed based on case-searching, and blood samples were collected from 409 residents. In total, 50 chronic KD cases were identified with a total prevalence of 9.3/10 000 population. The prevalence in the Tangyuan County was the highest (250/10 000 population). The mean serum SELENOP level was 13.96 mg/l. The spatial regression analysis showed that KD prevalence positively correlated with SELENOP levels and negatively with per capita disposable income among rural residents. Conclusions: The Tangyuan County should be considered for the precise prevention and control of KD. Further research is necessary to verify the reliability of SELENOP for estimating body selenium levels, and to better understand the relationship between selenium intake and KD in the investigated area. Int J Occup Med Environ Health. 2021;34(5):659–66