Objective To investigate the screening and diagnostic values of the parameters of erythrocyte and reticulocyte for hereditary spherocytosis. 〖WTHZ〗Methods A total of 41 patients with HS diagnosed in our hospital from January 2010 to December 2021 were selected. T test was used to compare the differences of HS group with autoimmune hemolytic anemia (AIHA)group, thalassemia (THAL)group and normal control group. Receiver Operator Characteristic (ROC) curve was used to analyze the screening and diagnostic values of the parameters of erythrocyte and reticulocyte for HS. Results MCV, MRV, MSCV and MSCV-MCV in HS group were significantly lower than those in AIHA group (P<0.05), while MCHC was significantly higher than that in AIHA group (P<0.05). ROC curve analysis showed that the cut-off value of MCHC for HS diagnosis was 338.5g/L, with the sensitivity of 94.6% and specificity of 73.7%. The cut-off value of MRV was 97.1fL, with the sensitivity of 91.9% and specificity of 86.9%. The cut-off value of MSCV-MCV was -3.4fL, with the sensitivity of 94.6% and specificity 89.4%. The area under the curve (AUC) of MRV combined with MCHC and MRV combined with MSCV-MCV were 0.978 and 0.988, respectively, which were greater than the AUC of any index of MCHC, MRV and MSCV-MCV. Conclusion MCHC, MRV, MSCV and MSCV-MCV have important reference values for the differential diagnosis of HS. MCHC is not an ideal indicator for screening and diagnosis of HS while MRV and MSCV-MCV have higher predictive values, and the combination of two of them is more effective than the single indicator