Objective: To compare the mutation status of epidermal growth factor receptor (EGFR) between different lesions and clini-cal characteristics of synchronous multiple ground-glass nodules (SMGGNs). Methods: A retrospective analysis was conducted using clinical data from 35 patients with SMGGNs who were admitted to and received surgery at The Fourth Hospital of Hebei Medical Uni-versity Hospital from January 2017 to December 2018. Next generation sequencing (NGS) was performed for all surgical specimens to detect the mutation status of exons 18, 19, 20, and 21 of the EGFR gene to analyze the relationship between the EGFR mutation sta-tus of the lesions and patient gender, age, lesion location, imaging manifestation of nodules, and adenocarcinoma pathological type . Results: The EGFR mutation rate was 65.7% (23/35 patients). Non-smoking patients and females had higher EGFR mutation rates (P=0.015, P<0.001). The EGFR mutation rate of invasive adenocarcinoma nodules was higher than those of atypical adenomatous hyper-plasia, adenocarcinoma in situ, and minimally invasive adenocarcinoma ( P<0.001). Exon 19 deletion and L858R mutation were the most common mutations of the EGFR gene. There was no significant difference between the pathological subtypes of adenocarcino-ma and the EGFR mutant subtype (P=0.707). Among the 27 patients with multiple nodules with detectable EGFR mutations, the EGFR mutation rate was 85.2% (23/27 patients). Conclusions: The EGFR gene mutation status is different in patients with multiple pulmo-nary ground-glass nodules, suggesting that the occurrence and development of each nodule are independent events. EGFR gene muta-tion is closely related to the development of ground-glass nodules, especially in the invasion of tumors.