Objective To investigate the relationship between the absolute count of peripheral blood lymphocytes (ALC) and the clinical characteristics and the effect of R-CHOP Regimen in elderly patients with diffuse large B-cell lymphoma (DLBCL). Methods The relevant data of 65 elderly patients with DLBCL treated in the department of Hematology, Guangyuan Central Hospital from January 2017 to February 2021 were retrospectively analyzed. DLBCL was diagnosed by histopathology and successfully received R-CHOP chemotherapy for ≥4 courses. According to the ALC level at the time of diagnosis of DLBCL, the selected patients were divided into low ALC group (ALC＜1.0×10 9/L, n=51) and high ALC group (ALC≥1.0×10 9/L, n=76), sort out and compare the differences of a series of clinical characteristic indexes between ttwo groups. According to the efficacy evaluation results after four courses of chemotherapy, the selected patients were divided into remission group (complete remission+partial remission, Cr+PR,n=92) and non remission group (stable+progress, SD+PD,n=35), and the correlation between ALC level and the chemotherapy effect of RCHOP Regimen was analyzed. Results The proportion of clinical stage Ⅲ~Ⅳ and IPI score 3~5 in low ALC group was significantly higher than that in high ALC group (P＜0.05). There was a significant negative correlation between ALC level and IPI score before chemotherapy (r=0.720, P＜0.05). The remission rate of R-CHOP Regimen in low ALC group was 60.78%, which was significantly lower than 80.26% in high ALC group (P＜0.05). Binary logistic regression analysis showed that clinical stage Ⅲ~Ⅳ (OR=1.691, 95%CI:1.147~2.540), IPI score 3~5 (OR=2.457, 95%CI:1.561~3.713) and ALC＜1.0×10 9/L (OR=1.803, 95%CI: 1.283~2.615) were independent risk factors affecting the effect of R-CHOP Regimen (P＜0.05). Conclusion ALC is not only closely related to the clinical stage and risk stratification of elderly DLBCL patients, but also the reduction of ALC is a risk factor affecting the effect of R-CHOP chemotherapy.