Carriers of α-thalassemia exhibit hypochromic microcytosis with mean corpuscular volume (MCV) < 80 fL, mean corpuscular hemoglobin (MCH) < 27 pg, and reduced hemoglobin A (HbA). We studied the distribution and diagnostic efficiencies of these indicators and their combinations in patients with and without alpha-thalassemia. Based on genetic diagnosis, 10,883 participants were divided into alpha-thalassemia group (n = 1655) and negative-for-alpha-thalassemia group (n = 9228). Erythrocyte parameters and hemoglobin analysis of the groups were analyzed. Moreover, we compared the four screening schemes (MCV/MCH, MCV/MCH/HbA, MCV + MCH, MCV + MCH + HbA) to find the best for α-thalassemia screening. The genotypes of --/αα, and -α/αα are the most prevalent with 54.9% and 27.6% in Fujian Province, China. There were significant differences in the distribution of MCV, MCH, and HbA in the two groups. Among the three, MCH exhibited the highest sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy. Although the four screening schemes have their advantages, there are significant differences in their sensitivity and specificity. MCV + MCH had the best diagnostic performance (72.6% sensitivity, 89.0% specificity) as well as the highest Youden index (61.59%). Our results showed that MCH could be used to screen α-thalassemia instead of MCV and HbA. However, it is recommended that MCV/MCH/HbA screening be used in areas with high α-thalassemia incidence to increased sensitivity.