Objective To assess the frailty status in elderly patients with non-operative stage Ⅲ epidermal growth factor receptor (EGFR) mutation-positive non-squamous non-small cell lung cancer (NSCLC) who were treated with sequential chemoradiotherapy followed by osimertinib treatment, and in those with stage Ⅳ NSCLC who were treated with stereotactic body radiotherapy (SBRT) combined with osimertinib, and analyze the influencing factors. Methods A retrospective analysis was conducted on 238 elderly patients with stage Ⅲ-Ⅳ EGFR mutation-positive non-squamous NSCLC admitted to the Shanxi Province Cancer Hospital from June 2020 to December 2021. After 3 continuous months of targeted osimertinib maintenance therapy, Numerical Rating Scale (NRS) score, Caprini risk assessment model for venous thromboembolism (Caprini) score, patient health questionnaire-9 (PHQ-9) score, geriatric 8 (G8) score were applied to these participants. According to their G8 score, they were divided into frail group(n=197) and non-frail group (n=41). SPSS statistics 19.0 was used to perform the statistical analysis. Student′s t test, Chi-square test, or Fisher exact test was employed for intergroup comparison depending on data type. And the related risk factors were identified by logistic regression analysis. Results The frailty group had higher proportion of advanced age, risk of high Caprini score and above, comorbidity; lower proportion of venous thromboembolism (VTE); higher depression level, NRS score and serum cystatin C level, but lower G8 score when compared with the non-frail group (all P<0.05). Logistic regression analysis indicated that age (OR=1.395,95%CI 1.133-1.717), depression level (OR=1.525,95%CI 1.290-1.803), NRS score (OR=7.908,95%CI 2.301-27.181), comorbidity (OR=5.490,95%CI 1.181-25.522), VTE (OR=7.530,95%CI 1.022-55.501), and serum cystatin C level (OR=1.215,95%CI 1.084-1.361) were risk factors for frailty status in the elderly patients with non-operative stage Ⅲ-Ⅳ EGFR mutation-positive non-squamous NSCLC. Conclusion Frailty is quite common among the elderly patients with non-operative stage Ⅲ-Ⅳ EGFR mutation-positive non-squamous NSCLC. They are characterized with kidney injury, and geriatric syndrome, such as nutrient loss, pain, impaired physical activity and cognitive ability, negative emotion and comorbidities. It is of great significance for early and rapidly identifying the influencing factors and implementing effective rehabilitation and treatment measures for these patients.