BACKGROUND: The immune system is linked to the prognosis and response to treatment of patients with cancer. However, the clinical implication of peripheral blood immune cells in cholangiocarcinoma (CCA) remains vague. Thus, we aimed to assess whether peripheral circulating immune cells could be used as an indicator for prognosis and chemotherapeutic efficacy in CCA. METHODS: The distributions of immune subsets were analyzed in peripheral blood samples from 141 patients with CCA and 131 healthy volunteers by using flow cytometry. The variation in the subset distribution in the two groups and the relationship between clinicopathological features and the subpopulations were investigated. Meanwhile, we assessed the implications of lymphocyte subsets as predictors of chemotherapy outcomes and overall survival (OS). RESULTS: The proportion of total lymphocytes decreased, while the percentages of activated T cells as well as CD4 CONCLUSION: The relationship between circulating immune cells with prognosis and chemotherapy response in patients with CCA highlights their potential application as an indicator of CCA prognosis and stratification of chemotherapy response.