Objectives: Few studies focused on the effects of radiation for different metastatic sites or radiotherapy doses on immune cell subsets. Therefore, this study investigated the effect of different irradiation doses and sites on the systemic immunity of patients with lung cancer. Method: Peripheral blood samples from 48 patients with lung cancer were collected, and the lymphocyte subsets were examined by flow cytometry. Results: In patients with non-small cell lung cancer (NSCLC) who received thoracic radiotherapy, the percentage of B lymphocytes after 20 fractions of radiotherapy was significantly lower than that recorded after 10 fractions (P=0.0046). In addition, the CD4+ naïve T-cell subsets at each different detection time point were significantly lower than the baseline (P=0.0304, <0.0001, <0.0004, respectively). In NSCLC patients with brain metastases who received brain radiotherapy, the percentage of B lymphocytes was significantly lower than the baseline (P=0.039). In patients with SCLC who received radiotherapy for the primary tumor, the percentage of CD4+ naïve T-cell subsets after 20 fractions was significantly lower than that observed after 10 fractions of radiotherapy (P=0.0444). There was no significant difference in other lymphocyte subsets at different time points or irradiated sites. Conclusion: Radiotherapy has a certain immunosuppressive effect. In addition, thoracic radiotherapy has an inhibitory effect on the proportion of T cells, whereas it does not significantly affect the proportion of T cells when irradiation of metastatic sites. It is suggested that the dose of radiotherapy in other metastatic organs of patients with lung cancer needs to be further escalated.