Purpose: In our study the diagnostic role of HMGB1 levels measured in serum were investigated in prostatitis and prostate carcinoma diagnosis and in the differential diagnosis of these two diseases. Material Method: Patients followed up for histopathologically verified diagnosis of prostate carcinoma and prostatitis in 20142017 at the Urology Clinic were included. HMGB1 measurement in serum was performed with the ELISA method. Results: A total of 78 subjects were included in the study, consisting of 30 (38.5%) prostatitis patients, 25 (32%) prostate carcinoma patients and 23 (29.5%) healthy subjects. HMGB1 was detected as 11.9±2.6 (Range 6.7-18.4) ng/ml in the prostatitis group, 15.1±4.5 (Range 8.4-24.8) ng/ml in the prostate carcinoma patients and as 9.2±3.1 (Range 4.7-18.7) ng/ml in the control group. The difference between the groups were investigated using the Friedman test as HMGB1 did not show normal distribution. Significant difference was detected between the three groups (p<0.001). When the groups were compared in pair, significant difference was detected between the prostatitis group and the control group (p=0.001). Significant difference was again detected between the prostate carcinoma group and the control group (p<0.001). Significant difference was detected between the prostatitis group and the prostate carcinoma group (p=0.006). Measurement of serum total prostate specific antigen (tPSA) levels were conducted automatically with the electro chemiluminescent method. A moderate level of (r=0.276) but a highly significant (p=0.009) positive correlation was found between PSA and HMGB1. Conclusion: In our study we showed that high PSA and high HMGB1 were highly correlated. HMGB1 measured in serum could be a useful marker in the differentiation of prostatitis and prostate carcinoma, in the early diagnosis of suspected prostate carcinoma and that HMGB1 value was significantly high in prostate carcinoma patients.