BK virus (BKV) is one of the most common pathogens in post-transplantation infections. For kidney transplantation, BKV infection results in the impairment of allograft function and thus increases the risk of allograft loss. However, clinical evaluation of the prognosis of BKV-associated allograft impairment is difficult. In the present study, differential plasma proteins were screened using proteomic methods from ten patients with a transition from BKV-negative to BKV activation. We identified 12 differentially expressed proteins, and S100A8 and S100A9 were the top two upregulated proteins. Data from a cross-sectional study with 66 BKV-negative and 66 BKV-positive recipients of renal transplantation indicated that plasma S100A8/A9 was upregulated in BKV-infected recipients. Plasma S100A8/A9 positively correlated with the 1 month creatinine increase (ρ = 0.499, P = 0.021) and negatively correlated with the 1 month estimated glomerular filtration rate change (ρ = -0.618, P = 0.003) in recipients with BK viremia. Using least absolute shrinkage and selection operator regression models, we found that S100A8/A9 was an independent risk factor for the decrease in allograft function after BKV infection. In conclusion, S100A8/A9 is a potential host biomarker for the clinical evaluation of BKV-associated allograft function impairment in kidney transplantation.