Objective To explore the influencing factors of cancer burden and cancer symptoms in the elderly patients with lung cancer during targeted therapy. Methods A retrospective analysis was made of clinical data of 98 elderly lung cancer patients who received targeted therapy at Suzhou Kowloon Hospital, School of Medicine, Shanghai Jiao Tong University from January 2019 to December 2022. The cancer burden and symptom distress were assessed by self-perceived Burden Scale (SPBS) and symptom distress scale (SDS) three months after treatment. The SPBS and SDS scores of the patients with different clinical characteristics were compared, and multivariate logistic regression was used to analyze the risk factors affecting SPBS and SDS scores in the elderly lung cancer patients during targeted therapy. SPSS statistics 22.0 was used for statistical analysis. Data comparison between two groups was performed using t test or F test depending on data type. Results The SPBS scores of 98 elderly lung cancer patients during targeted therapy were 13-26 (19.34±6.28) points, and the SDS scores were 23-40 (31.57±8.19) points. The elderly lung cancer patients with stage Ⅲ-Ⅳ of tumor node metastasis (TNM), over three comorbid chronic diseases, self-funded medical payment, monthly income < 2 000 yuan, low social support and low family care had higher SPBS scores during targeted therapy than those with stage Ⅰ-Ⅱ of TNM, three or fewer comorbid chronic diseases, free medical payment or partial reimbursement, and monthly income ≥2 000 yuan, medium or high social support, and medium or high family care, and the difference was statistically significant (P<0.05). The elderly lung cancer patients with stage Ⅲ-Ⅳ of TNM, over three comorbid chronic diseases, low social support and low family care during targeted therapy had higher SDS scores than those with stage Ⅰ-Ⅱ of TNM, three or fewer comorbid chronic diseases, medium or high social support, medium or high family care, and the difference was statistically significant (P<0.05). Multivariate logistic regression analysis confirmed that stage Ⅲ-Ⅳ of TNM, over three comorbid chronic diseases, self-funded medical payment , monthly income < 2 000 yuan, low social support, low family care were the risk factors of SPBS score in the patients (P < 0.05), and that stage Ⅲ-Ⅳ of TNM, over three comorbid chronic diseases, low social support and low family care were the risk factors of SDS score (P<0.05). Conclusion SPBS and SDS scores in the elderly lung cancer patients during targeted therapy were affected by multiple factors, such as TNM stage, number of comorbid chronic diseases, social support, and family care. Clinicians should try to identify and pay attention to them during the treatment of the disease.