Objective: To investigate the clinical effect of platelet-rich fibrin (PRF) in the treatment of chronic wounds combined with subcutaneous stalking sinus caused by various kinds of reasons. Methods: The clinical data of 72 patients with chronic wounds and combined with subcutaneous stalking sinus caused by various kinds of reasons admitted to our unit from June 2015 to February 2017, conforming to the study criteria, were collected and retrospectively analyzed. Patients were divided into group PRF (n=39) and routine dressing change (RDC) group (n=33) according to their treatment. The subcutaneous stalking sinuses of patients in group PRF were filled with PRF 1 or 2 times after debridement, while the surface of wound was covered by vaseline gauze and aseptic dressing, and dressing change was performed once per 2-3 days. The wounds of patients in group RDC were filled with iodine gauze after debridement of wounds and wrapped up with conventional aseptic dressing, and dressing change was performed once per 0.5-2.0 days. The times of operation, the times of dressing change, the time for negative-conversing of bacteria culture in the secretion of wound, the time of subcutaneous stalking sinus closure, and the complete healing time of wounds of patients in two groups were recorded. Data were processed with Chi-square test and independent sample t test. Results: The operation times of patients in two groups were close (t=0.565, P>0.05). The dressing changes of patients in group PRF were (6.4±2.1) times, significantly less than (19.2±6.2) times in group RDC, t=12.107, P<0.01. The time for negative-conversing of bacteria culture in the secretion of wound of patients in group PRF was (15±5) d, significantly shorter than (25±9) d in group RDC, t=6.087, P<0.01. The time of subcutaneous stalking sinus closure of patients in group PRF was (12±5) d, significantly shorter than (24±8) d in group RDC, t=7.315, P<0.01. The complete healing time of wounds of patients in group PRF was (23±7) d, significantly shorter than (35±10) d in group RDC, t=5.924, P<0.01. All the chronic wounds of patients in two groups were completely healed, and there were no break or new sinus formed during the follow-up of 4-12 months after discharge. Conclusions The application of PRF in the treatment of chronic wounds combined with subcutaneous stalking sinus caused by various reasons can bring about rapidly healing of wounds, definite effect, and convenient operation, thus is worth promoting and applying in clinic.