Neoadjuvant chemoradiotherapy is one of the standard treatments for patients with locally advanced rectal cancer (LARC). However, only about 15%~20% of patients with rectal cancer experienced pathologic complete response (pCR) after neoadjuvant therapy, while partial tumor regression was observed in most patients, and even some patients could not benefit from neoadjuvant therapy. Therefore, how to identify patients with ineffective or potentially complete response to neoadjuvant chemoradiotherapy (nCRT) is crucial for the individualized diagnosis and treatment of locally advanced rectal cancer. An increasing number of studies have actually focused on the discovery and investigation of new biomarkers for predicting pCR reactions. Circulating biomarkers refer to substances in peripheral blood including cells, nucleic acids, extracellular vesicles, proteins and metabolites, etc., which have sufficient sensitivity and specificity and are related to the severity of the disease, and can observe prognostic or predictive biomarker effects. In this review, we review the value of blood-based circulating biomarkers that potentially predict neoadjuvant efficacy in LARC patients.