Various immunologic and inflammatory factors are contributed to pathogenesis of Parkinson's disease (PD). High mobility group box-1 (HMGB1) is a protein that plays certain roles in inflammation, DNA repair, transcription, somatic recombination, cell differentiation, cell migration, neuronal development, and neurodegeneration. The aim of the present study was to evaluate the serum levels of HMGB1 and high-sensitivity C-reactive protein (hs-CRP) among patients with Parkinson's disease and healthy controls. This study includes 30 patients with PD and 30 healthy controls, matched sex, age, body mass index, and smoking status. HMGB1 and hs-CRP serum levels were compared between the groups. The diagnostic performance of HMGB1 and hs-CRP was evaluated with receiver operating characteristic (ROC) curve analysis. HMGB1 levels were significantly higher in PD patients than in controls. Hs-CRP levels were significantly higher in PD patients than in controls There was a moderate correlation between hs-CRP and HMGB1 levels in the patient group. The cut-off value of HMGB1 level for the prediction of PD was determined as 32.8ng/mL with 80% sensitivity and 60% specificity (p=0.006). The cut-off value of hs-CRP level for the prediction of PD was determined as 0.63mg/L with 66.7% sensitivity and 77.7% specificity (p=0.007). This study demonstrates for the first time the association between HMGB1, hs-CRP, and PD. We found that HMGB1 and hs-CRP levels to be significantly higher in the PD patients than in the normal controls. As a result of the ROC curve analysis, HMGB1 and hs-CRP levels may be fair markers in the diagnosis of PD.