Low vitamin D status is associated with an increased risk of renal cell carcinoma (RCC). This study investigated the association of vitamin D status with serum C-reactive protein (CRP) and adhesion molecules among RCC patients. Fifty newly diagnosed RCC patients and 100 age- and sex-matched controls were recruited. As expected, serum 25(OH)D level was lower in RCC patients than in controls. By contrast, serum levels of CRP, an inflammatory molecule, and ICAM, LAMA4 and EpCAM, three adhesion molecules, were higher in RCC patients than in controls. All RCC patients were divided into two groups: H-VitD (>20 ng/ml) or L-VitD (<20 ng/ml). Interestingly, the levels of serum CRP and all adhesion molecules were higher in RCC patients with L-VitD than those with H-VitD. Nuclear vitamin D receptor (VDR) was downregulated and nuclear factor kappa B (NF-κB) was activated in cancerous tissues. The in vitro experiments found that VitD3 suppressed NF-κB activation and adhesion molecules in RCC cells. Moreover, VitD3 suppressed NF-κB through reinforcing physical interaction between VDR and NF-κB p65 subunit in RCC cells. These results provide a mechanistic explanation for the association among low vitamin D status, local inflammation and increased expression of adhesion molecules among RCC patients.