Abstract: Objective: This clininal study investigated whether daily pretreatment with ambroxol (A) could reduce the incidence of acute and chronical lung toxicity. Methods: Patients(n=139) with radiotherapy (RT) received a daily fraction of 1.8-2.0Gy/5days/week in an approximately total of 60 Gy with or without ambroxol 2-3mg/kg/day oral intake three times/day for 3 months, starting on the first day of radiotherapy. Acute and chronical toxicities were graded from 0 to 4 according to RTOG. Results: The patients (n=139) were evaluated, 3 months post-RT for the incidence of pneumonitis: 50.0% of patients in the RT group and 23.3% in the RT+A group experienced ≥ Grade 2 pneumonitis, there was a significant difference between 2 groups. At 6, 12 and 18 months, fibrosis was present in 54.1%, 55.5% and 50.0% receiving RT vs.27.3%, 25.8% and 22.6% receiving RT+A; there was a significant difference between them. Conclusion: Ambroxol reduced the incidence of pneumonitis and fibrosis for the patients in radiotherapy with local advanced lung cancer, without compromising anti-tumor efficacy.