Background: Oral targeted therapy is increasingly used worldwide to treat patients with advanced lung cancer. The adverse skin toxicity that is associated with treatment with epidermal growth factor receptor inhibitors often results in acneiform rash, dry skin (xerosis), pruritus, and paronychia, which may cause discomfort in patients and affect their quality of life. Purpose: This study was designed to explore changes in skin toxicity and quality of life (measured overall by three subscales) as well as the correlation between skin toxicity and overall quality of life over a 3-month period for patients with advanced lung cancer receiving oral targeted therapy. Methods: This study used a longitudinal research design. Baseline data were collected before initiating targeted therapy. Data for the effects of targeted therapy on skin toxicity and quality of life were collected at 2, 4, 8, and 12weeks after therapy initiation. Data on skin toxicity were collected using the Common Terminology Criteria for Adverse Events Version 4.03, and quality of life was measured using the Chinese version of the Functional Assessment of Cancer Therapy-Epidermal Growth Factor Receptor Inhibitor-18 questionnaire. Demographic and clinical data were analyzed using descriptive statistics, and Spearman's rank correlation coefficient was used to measure the correlation between skin toxicity and quality of life. Results: Thirty-two patients participated in this study. The symptoms of skin toxicity that increased over the 3-month study period included xerosis and paronychia, whereas acneiform rash and pruritus fluctuated during this period. Over the study period, more than 70% of the participants exhibited symptoms of skin toxicity. Skin toxicity was the greatest and quality of life was the lowest, respectively, at the end of the study. All of the symptoms of skin toxicity were significantly correlated with quality of life, although each varied over time (r = .36–.61, p < .05). Conclusions/Implications for Practice: The results of this study indicate that healthcare providers should consider the impact of skin toxicity on quality of life in patients with advanced lung cancer who are receiving oral targeted therapy. These findings may be used to design interventional measures for skin and medical care to improve quality of life in patients with advanced lung cancer.