Objective A retrospective study was conducted by developing prediction models to evaluate the association between hematological indexes, their changes during neoadjuvant chemoradiotherapy (NCRT), and tumor pathological response in patients with locally advanced rectal cancer. Methods The clinical data of 202 patients who received NCRT and radical surgery in Sichuan Cancer Hospital were retrospectively analyzed. Univariate and logistic multivariate regression analyses were used to identify hematological indexes with predictive significance. The independent risk factors were imported into the R software, and a nomogram prediction model was developed. The bootstrap method and ROC curve were used to evaluate the discriminative degree of the model. Results Univariate analysis demonstrated age, tumor diameter, preoperative T, distance from tumor to the anal verge, CEA before NCRT, preoperative CEA, lymphocyte changes, platelet changes, and pathology of rectal cancer after NCRT were associated. Multivariate analysis demonstrated that age, tumor distance from the anus, preoperative CEA, lymphocyte changes, and platelet changes were independent risk factors. The independent risk factors were imported into the R software to construct a nomogram model. The area under the ROC was 0.76, and the slope of the calibration curve of the nomogram was close to 1. Conclusion A low preoperative CEA level, a young age, a high tumor from the anal verge, the maintenance of circulating lymphocyte level, and a decreased platelet level after NCRT are important factors for favorable outcomes after NCRT. Developing a nomogram prediction model with good discrimination and consistency can provide some guidance for predicting pathological responses after NCRT.