Background: Cholangiocarcinoma is a malignant neoplasia that originates in the bile ducts. Most patients with cholangiocarcinoma are inoperable at the time of diagnosis. photodynamic therapy (PDT) is a fairly well accepted treatment in clinical practice for nonresectable cholangiocarcinoma (NCC) but lack of quantitatively assessment. Herein, we present a protocol for a systematic review to identify the efficacy of PDT in patients with NCC. Methods: We will search PUBMED, SpringerLink, Cochrane Library, the Chinese Biomedical database (CBM), WanFang data, China National Knowledge Infrastructure (CNKI) up to December 2017. Studies will be screened by title, abstract, and full text independently and in duplicate. Studies that report PDT in patients with nonresectable cholangiocarcinoma will be eligible for inclusion. Outcome variables will be assessed included survival benefit, health status and quality of life, and adverse events with photodynamic therapy. Assessment of risk of bias and data synthesis will be performed using Revman software. The hazard ratios will be extracted from the survival curves using Tierney Method. Heterogeneity among studies will be assessed using the I2 statistic. Results: This study will review randomized controlled trials, cohort studies, or retrospective studies and quantitatively assess the efficacy of PDT in patients with NCC for the latest evidence-based recommendation. Conclusion: This study will evaluate therapeutic effect of PDT in patients with NCC systematically. We expect that the results from this systematic review for clinical trials will help inform clinical practice in NCC.