The aim of this study was to investigate the role of chromatin assembly factor 1 subunit A (CHAF1A) in the pathogenesis of non-small cell lung cancer (NSCLC), as well as its association with disease prognosis. The expression levels of CHAF1A in NSCLC tissues were detected by immunohistochemical staining. The relationship between CHAF1A and patient survival was analysed. The effects of CHAF1A knock-down on cell proliferation, cell cycle, cell clones and cellular apoptosis were also analysed. The results showed that CHAF1A staining was observed in the cell nuclei in the NSCLC tissue, with higher H-score. In the CHAF1A low-expression group, the 5-year survival rate was significantly higher and the recurrence rate was significantly lower compared with the high-expression group. Tumour size, lymph node metastasis, clinical staging and H-score represented influencing factors related to the 5-year survival. CHAF1A expression was significantly associated with the 5-year overall survival and metastasis and recurrence of NSCLC. In addition, CHAF1A knock-down inhibited the proliferation and changed the cell cycles, cell clones and cellular apoptosis in the lung cancer cells. The results indicated that higher CHAF1A expression is related to shortened survival period of NSCLC, and CHAF1A knock-down inhibited the proliferation of lung cancer cell lines. CHAF1A might represent a disease prognostic predictor in clinic.