Liquid biopsy has advantages over traditional biopsy, which cannot determine tumor dynamics. As a noninvasive and precise test, liquid biopsy detects biomarkers that carry information on tumor progression and has undergone tremendous development in recent years. Exosome detection is one of the methods of liquid biopsy. Radiotherapy affects the release of exosomes and intercellular communication. Based on the properties, extractability, and detectability of exosomes, key exosomal cargoes after tumor radiotherapy can be used as biomarkers for tumor prognosis. Exosomes after tumor radiotherapy can be used for liquid biopsy. The main applications include (1) predicting radiotherapy efficacy, (2) predicting tumor prognosis, and (3) optimizing the regimen of tumor treatment. This review provides further research directions for liquid biopsy after tumor radiotherapy.