Abstract: OBJECTIVE To investigate the relationship between expression of C-type lectin receptors (CLRs) in peripheral blood mononuclear cells (PBMCs) and secondary invasive fungal infection (IFI) in the lung after radiotherapy for lung cancer patients. METHODS A total of 65 patients with secondary lung IFI after lung cancer radiotherapy admitted to Sichuan Armed Police Corps Hospital between Jan. 2018 and Mar. 2021 were retrospectively selected as the study subjects and set as the IFI group, anther 40 patients without IFI after radiotherapy for lung cancer admitted to the hospital during the same period were collected and set as control group. The distribution of pathogens in the IFI group were detected, and the expression levels of DC-associated C-type lectin receptors 1 (Dectin1), Dectin2 and DC specific intercellular adhension molecule-3 grabbing non-integrin (DC-SIGN) in PBMCs between the two groups were compared. The relationship between Dectin1, Dectin2, DC-SIGN and secondary lung IFI after radiotherapy in lung cancer patients was analyzed by multivariate regression analysis and receiver operating characteristic (ROC) curves analysis. RESULTS A total of 76 strains of pathogens were isolated from 65 patients with secondary lung IFI after lung cancer radiotherapy, mainly Candida albicans (48.68%), Candida tropicalis (18.42%) and Aspergillus (14.47%). There were significant differences in tumor stage, invasive operation, preventive usage of antibiotics, diabetes mellitus, CD₄⁺/CD₈⁺ and hospitalization time of patients between IFI group and control group (P<0.05). The relative expression levels of Dectin1, Dectin2 and DC-SIGN mRNA in PBMCs in the IFI group were higher than those in the control group (P<0.05). The area under the ROC curve (AUC) of Dectin1, Dectin2 and DC-SIGN alone for predicting lung IFI secondary to radiotherapy for lung cancer was lower than that of combined detection (P<0.05). CD₄⁺/CD₈⁺ <1.3, invasive operation, Dectin1 >22.68, Dectin2 >14.72 and DC-SIGN >16.95 were risk factors of secondary pulmonary IFI after radiotherapy in lung cancer patients (P<0.05). CONCLUSION Dectin1, Dectin2 and DC-SIGN were highly expressed in PBMCs of patients with pulmonary IFI secondary to lung cancer radiotherapy, and the combined detection of the three indicators had good predictive value for the occurrence of pulmonary IFI after lung cancer radiotherapy.