Objective To investigate the correlation of cofilin1 and its phosphorylation at serine-3 (Ser3) with the radiotherapy sensitivity of elderly patients with non-small cell lung cancer (NSCLC).Methods A total of 102 elderly patients pathologically confirmed NSCLC, who were treated with surgical resection and postoperative radiotherapy in our hospital between June 2013 and April 2015, were selected in this study. According to their efficacy, patients were divided into radiotherapy-sensitive group (55 cases) and radiotherapy-resistant group (47 cases). The expression of cofilin1 and its Ser3-phosphorylated protein—cofilin1 (phospho S3) were detected. The survival time and survival rate of all patients were recorded.Results The radiotherapy-resistant group had higher TNM staging and rate of lymph node metastasis than the radiotherapy-sensitive group (P<0.05). The cofilin1-positive group also had higher TNM staging and lymph node metastasis rate than the cofilin1-negative group (P<0.05), while the cofilin1 (phospho S3)-positive group had lower TNM staging and lymph node metastasis rate than the cofilin1 (phospho S3)-negative group (P<0.05). The positive expression rate of cofilin1 was higher in the radiotherapy-resistant group than in the radiotherapy-sensitive group, and the positive expression rate of cofilin1 (phospho S3) was higher in the radiotherapy-sensitive group than in the radiotherapy-resistant group (P<0.05). Lymph node metastasis, high expression of cofilin1, and low expression of cofilin1 (phospho S3) were independent predictors of radiotherapy resistance (P<0.05). The progression-free survival (PFS) was longer and the 5-year survival rate was higher in the radiotherapy-sensitive group, cofilin1-negative group, and cofilin1 (phospho S3)-positive group (P<0.05). In the radiotherapy-sensitive group, patients with negative cofilin1 and positive cofilin1 (phospho S3) had the longest PFS and the highest 5-year survival rate (P<0.05). In the radiotherapy-resistant group, patients with positive cofilin1 and negative cofilin1 (phospho S3) had the shortest PFS and the lowest 5-year survival rate (P<0.05).Conclusion The radiotherapy sensitivity of elderly NSCLC patients is significantly negatively correlated with cofilin1 and positively correlated with the phosphorylation level at Ser3 of cofilin1. Cofilin1 and its phosphorylation at Ser3 are independent predictors of the sensitivity to radiotherapy, and they are of great significance in the prognosis assessment of elderly NSCLC patients.