Background and objective <p>Several studies have reported the prognostic significance of blood cells in patients with esophageal squamous cell carcinoma (ESCC); however, the relationship between blood cells and the efficacy and prognosis of neoadjuvant immunotherapy combined with chemotherapy in the treatment of ESCC has not been evaluated.In this study, we aimed to elucidate the predictive value of response and prognostic value of peripheral blood cells for neoadjuvant immunotherapy combined with chemotherapy in patients with ESCC.</p> Methods <p>A total of 91 patients with ESCC (clinical stage II–IVA) who underwent neoadjuvant immunotherapy combined with chemotherapy (nICT) followed by surgery were enrolled in this study. A comparative analysis was performed to determine whether the pathological response after treatment was pathological complete response (PCR) and to establish the pathological regression grading.</p> Results <p>The pathological complete response rate (PCR) was 22%, and more than half (52%) of the tumor regression grades assessed after neoadjuvant therapy responded well demonstrating significant tumor regression. A pathological complete response was strongly associated with the number of lymphocytes in the blood before treatment (<i>p</i> = 0.018). The efficacy response was strongly correlated with the number of erythrocytes in the blood before treatment (<i>p</i> = 0.011).Patients with a low red blood cell (RBC) count had a better 3-year disease free survival (DFS) than those with a high RBC(95.2% vs. 45.9%, <i>P</i> &lt; 0.05).</p> Conclusions <p>Pretreatmentment Lymphocytes ≥ 1.845 × 10⁹/L were found to have a good predictive effect on the PCR and RBCs &lt; 4.31 × 10¹²/L were reflective of better tumor regression grades. Therefore, RBCs &lt; 4.31 × 10¹²/L may serve as a surrogate marker of better prognosis in patients who have undergone nICT followed by esophagectomy.</p>