Objective: To explore the relevant factors of radiation-induced lung injury (RILI) caused by radiotherapy in patients with lung cancer. Methods: A total of 110 patients with lung cancer were treated with three-dimensional conformal radiotherapy (1.8–2.2 Gy, 1 time/d, 5 times/week in each time, 5–7 irradiation, and the total dose ≥ 56 Gy). All the related clinical factors of patients were collected; V5, V10, V15, V20, V30, V40 and average lung dose (MLD) of double lungs, ipsilateral lung the contralateral lung were recorded according to dose volume histogram (DVH) and planned target volume, the determination of serum IL-6, IL-8 and TGF-β1 level were determined before radiotherapy. The correlation between clinical factors and radiation physical parameters and RILI was observed, and the relevant factors of RILI were analyzed. Results: All patients successfully completed radiotherapy. Radiotherapy dosage, serum IL-8, TGF-β1 level in clinical factors were associated with RILI occurrence, and physical parameters of double lung V5, double lung V10, double lung MLD, side V5, the contralateral pulmonary lung V5 were associated with RILI occurrence, with the significant differences (P<0.01). The logistic multi-factors were analyzed, and the total dose radiation acuity ≥64 Gy, the contralateral lung V5 and IL-8 before radiotherapy were the relevant factors of RILI in patients with lung cancer received radiotherapy. Conclusion: The occurrence of RILI is the result of multiple factors interacting with each other. The total dose of radiotherapy ≥64 Gy, the contralateral lung V5, and the level of serum IL-8 before radiotherapy are the independent influencing factors of RILI in patients with lung cancer.