Objective. To analyze multiple factors developing lung adenocarcinoma lesion from solitary pulmonary nodule (SPN). Methods. A total of 70 patients diagnosed with lung adenocarcinoma after finding SPN by chest CT and treated in our hospital (01, 2018–01, 2021) were selected as the malignant lesion group, and another 70 patients diagnosed with benign lesion after finding SPN by CT in the same period were included in the benign lesion group. All patients had complete medical records. With univariate analysis and multivariate logistic regression, the independent risk factors for developing lung adenocarcinoma lesions from SPN were analyzed. Results. By conducting univariate analysis of patients’ general information (age, course of disease, BMI, nodule diameter, and gender), smoking status (smoking history and number of cigarettes smoked per year), medical history (family history of lung cancer, history of extrapulmonary malignant tumor, and history of autoimmune diseases), basic complications (hypertension and diabetes), and laboratory examinations (CEA, NSE, CYFRA21-1, SCC-Ag, and CA125), it was concluded that age, course of disease, nodule diameter, CEA positive, CYFRA21-1 positive, and CA125 positive were significantly different between the two groups (P < 0.05); the logistic regression results showed that high age, increased nodule diameter, and CYFRA21-1 positive were the independent risk factors developing lung adenocarcinoma from SPN (P < 0.05). Conclusion. In patients with SPN, higher age, longer course of disease, greater nodule diameter, and CYFRA21-1 positive imply increased risk for triggering lung adenocarcinoma lesion. Therefore, high attention should be paid in the clinic to such SPN patients for early diagnosis and treatment.