Residential greenness may decrease the risk for hyperuricemia in rural areas, but the urban-rural disparities in this association and underlying pathways have not been studied. To investigate the associations and potential pathways between residential greenness and hyperuricemia in urban and rural areas. The baseline survey of the China Multi-Ethnic Cohort (CMEC) was used. Hyperuricemia was defined as serum uric acid (SUA) > 417 μmol/L for men and >357 μmol/L for women. The satellite-based normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) were used to capture residential greenness. A propensity score inverse-probability weighting method was used to assess urban-rural differences in the associations between residential greenness and hyperuricemia, with possible mediation effects of physical activity (PA), body mass index (BMI), PM 2.5 , and NO 2 examined by causal mediation analyses. A total of 72,372 participants were included. The increases in the EVI 500m and NDVI 500m residential greenness were associated with a decreased risk for hyperuricemia and the SUA level in both urban and rural areas. For example, each 0.1-unit increase in EVI 500m was associated with a decreased hyperuricemia risk of 7% (OR = 0.93 [0.91, 0.96]) and a decreased SUA level of −1.77 μmol/L [-2.60, −0.93], respectively; such associations were stronger in urban areas for both the risk for hyperuricemia (OR = 0.84 [0.83, 0.86]) and SUA level (−7.18 μmol/L [-7.91, −6.46]). The subgroup analysis showed that the greenness-hyperuricemia/SUA association varied by age, sex, and annual household income. The percentage of the joint mediation effect of PA, BMI, PM 2.5 , and NO 2 on the association between EVI 500m and the risk for hyperuricemia was higher in urban (34.92%) than rural areas (15.40%). BMI, PM 2.5 , and PA showed significantly independently mediation effects for the greenness-hyperuricemia association in both rural and urban areas. Exposure to residential greenness was associated with a decreased risk for hyperuricemia, partially through the pathways of PA, BMI, PM 2.5 , and NO 2 , which varied in urban and rural areas. • We examined urban-rural differences in the associations between greenness and hyperuricemia. • More exposure to residential greenness was associated with a decreased risk for hyperuricemia. • The negative association between greenness and hyperuricemia was stronger in urban areas. • The greenness-hyperuricemia association varied by age, sex, and annual household income. • Physical activity, BMI, PM 2.5 , and NO 2 play mediation roles between greenness and hyperuricemia. [ABSTRACT FROM AUTHOR]