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Background and purpose: Perineural invasion is a prognostic factor in colorectal cancer. It is unclear whether perineural invasion is a prognostic factor in in node-negative (ypⅠ-Ⅱ) rectal cancer patients who received neoadjuvant radiotherapy because there may be varying degrees of tumor regression. This study aimed to investigate prognostic value of perineural invasion in node-negative rectal cancer patients who received neoadjuvant radiotherapy. Methods: A total of 5 222 patients who received neoadjuvant radiotherapy and were diagnosed with stage ypⅠ-Ⅱ rectal cancer from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018 were identified and clinicopathological features and cancer-specific survival outcomes were retrospectively analyzed. Chi-square analysis was used to compare clinicopathological features between two groups. Kaplan- Meier survival analysis and the log-rank test were used to estimate the 5-year cancer-specific survival. Multivariable Cox regression analyses were used to identify the independent prognostic factor. Results: Compared with patients without perineural invasion, patients with perineural invasion were more likely to be black, have elevated carcinoembryonic antigen (CEA), stage Ⅱ disease, tumor＜5 cm and poorer differentiated tumors (P＜0.05). Patients without perineural invasion had superior cancer-specific survival than those with perineural invasion (5-years survival rate: 85.3% vs 68.9%). The survival difference was more evident in patients with stage ypⅡ cancer. Multivariable Cox regression analyses demonstrated that perineural invasion was an independent prognostic factor in node-negative rectal cancer patients who received neoadjuvant radiotherapy. Conclusion: Perineural invasion is associated with oncological outcomes of node-negative rectal cancer patients who received neoadjuvant radiotherapy, thus it could serve as a prognostic factor in these patients. [ABSTRACT FROM AUTHOR]