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Objective To evaluate the efficacy and safety of pirfenidone combined with N-acetylcysteine （NAC） in the treatment of pulmonary fibrosis, aiming to provide basis for clinical medication. Methods Clinical data of 1 patient with combined pulmonary fibrosis and emphysema （CPFE） progressing into idiopathic pulmonary fibrosis （IPF） were reviewed. Relevant literature was searched and screened from PubMed using the keywords of “pirfenidone”and “N-acetylcysteine”. The extracted data and relevant literature were collected for retrospective analysis. Results The male patient, aged 70 years old, was clinically diagnosed with CPFE which progressed into IPF. In February, 2018, he was treated with pirfenidone combined with NAC. Pulmonary function indexes and CT scan data were improved. No significant adverse events were observed. High clinical efficacy was achieved. Six studies were retrieved in this study. The findings in 4 studies showed that the efficacy of pirfenidone combined with NAC was better than that of monotherapy in the treatment of pulmonary fibrosis. The results in the other 2 studies demonstrated that the disease progression rate of patients treated with pirfenidone combined with NAC was higher compared with that of pirfenidone alone. Conclusions Pirfenidone combined with NAC yield certain effect upon improving the lung function of IPF patients. Clinical efficacy of combined therapy is probably higher compared with that of monotherapy.