Background: In view of the limited knowledge of plasma biomarkers relating to cancer resistance to radiotherapy, we have set up screening, training and testing stages to investigate the microRNAs (miRNAs) expression profile in plasma to predict between the poor responsive and responsive groups after 6 months of radiotherapy. Methods: Plasma was collected prior to and after radiotherapy, and the microRNA profiles were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) arrays. Candidate miRNAs were validated by single qRT-PCR assays from the training and testing set. The classifier for ancillary prognosis was developed by multiple logistic regression analysis to correlate the ratios of miRNAs expression levels with clinical data. Results: We revealed that eight miRNAs expressions had significant changes after radiotherapy and the expression levels of miR-374a-5p, miR-342-5p and miR-519d-3p showed significant differences between the responsive and poor responsive groups in the pre-radiotherapy samples. The Kaplan-Meier curve analysis also showed that low miR-342-5p and miR-519d-3p expressions were associated with worse prognosis. Our results revealed two miRNA classifiers from the pre- and post-radiotherapy samples to predict radiotherapy response with area under curve values of 0.8923 and 0.9405. Conclusions: The expression levels of miR-374a-5p, miR-342-5p and miR-519d-3p in plasma are associated with radiotherapy responses. Two miRNA classifiers could be developed as a potential non-invasive ancillary tool for predicting patient response to radiotherapy.