Objective To explore the effect of epidermal growth factor receptor (EGFR) on the proliferation, apoptosis of lung cancer cells and related mechanisms.Methods Taking human normal bronchial epithelial cells 16HBE and lung cancer cells A549, H1299, MSTO-211H as the research objects, qRT-PCR and western blot were used to detect the levels of EGFR mRNA and protein in cells, respectively. MSTO-211H cells was divided into NG group, pcDNA3.1 group, pcDNA3.1-EGFR group, pcDNA3.1- EGFR+anti-IL-6 group、pcDNA3.1-EGFR+JSI-124 group. qRT-PCR was used to detect EGFR mRNA level; CCK-8 method and plate cloning experiment, Hoechst33342 staining method and flow cytometry were used to detect cell proliferation and apoptosis respectively. Western blotting was used to detect the changes of expression of EGFR, cell cycle protein D1 (CyclinD1), apoptosis-related protein B-cell lymphocyte-2 (Bcl-2), Bcl-2-associated X protein (Bax) and interleukin-6/signal transducer and activator of transcription 3 (IL-6/JAK/STAT) pathway related proteins. Results Compared with 16HBE cells, EGFR mRNA and protein expression levels in A549, H1299, and MSTO-211H were significantly increased, and EGFR mRNA and protein expression levels in MSTO-211H cells were the lowest. Therefore, MSTO-211H cells were selected for subsequent experiments; compared with the NG group and the pcDNA3.1 group, the apoptotic activity of MSTO-211H cells in the pcDNA3.1-EGFR group was significantly weakened, the cell proliferation inhibition rate, apoptosis rate, EGFR and Bax protein expression were significantly reduced (P＜0.05), the clone formation rate, CyclinD1, Bcl-2, IL-6, p-JAK/JAK, and p-STAT/STAT protein expression were significantly increased (P＜0.05); compared with the pcDNA3.1-EGFR group, the apoptotic of MSTO-211H cells in the pcDNA3.1-EGFR+anti-IL-6 group and pcDNA3.1-EGFR+JSI-124 group was significantly enhanced, the cell proliferation inhibition rate, apoptosis rate, and Bax protein expression were significantly increased (P＜0.05), the clone formation rate, CyclinD1, Bcl-2, IL-6, p-JAK/JAK, and p-STAT/STAT protein expression were significantly reduced (P＜0.05). Conclusion Overexpression of EGFR can promote the proliferation of MSTO-211H cells and inhibit cell apoptosis, which may be achieved by promoting the activation of IL-6/JAK/STAT signaling pathway.