Objective To investigate the value of transglutaminase 4 in diagnosis and prognosis prediction of prostate cancer. Methods Transglutaminase 4 immunostaining was performed with paraffin sections from 159 prostate cancer patients receiving radical prostatectomy, and the staining results were divided into 4 levels: negative staining, weak staining, moderate staining, and strong staining. The clinical and pathological information of the patients were obtained by reviewing the medical records. The follow-up data were collected by reviewing medical records, prostate cancer database of our department, and telephoning the patients or their family members. Expression of transglutaminase 4 and clinical, prognosis data of patients were subjected to statistical analysis. Results The expression of transglutaminase 4 in the prostatic cancer tissue was significantly higher than that in the adjacent normal tissue (P<0.001); and the expressions were significantly different in patients with different Gleason grades (P<0.001) and different prostate specific antigen levels(P=0.005). Univariate Cox regression analysis indicated that high transglutaminase 4 expression was a risk factor of biochemical recurrence of prostatic cancer (P=0.020), but multivariate Cox regression analysis did not support this finding (P=0.139). Conclusion Transglutaminase 4 expression is increased in prostate cancer tissues, and the expression is stronger in malignant tissues with higher Gleason grade and prostate specific antigen level.