Abstract: Objective　To measure the serum GDF15 levels, to explore the possible correlations between serum GDF15 levels to anemia severity, hematopoietic activity and iron parameters in various types of childhood anemia, and to investigate its clinical application in the differential diagnosis of severe beta thalassemia (SBT). Methods　Eighty-five children with various types of anemia were enrolled into this study, including 19 cases of IDA, 8 cases of ACD, 24 cases of AA, 17 cases of severe β-thalassemia (SBT) and 17 cases of hemolytic anemia other than SBT (non-SBT HA). In addition, 21 age- and sex- matched healthy children were recruited as controls. Serum GDF15 levels both in anemic and healthy control subjects were determined by GDF15 Quantikine DGD 150 ELISA assay. Correlations were made between GDF15 levels and Hb concentrations, reticulocyte indices and iron parameters. The diagnostic significance of serum GDF15 determination in the differential diagnosis of SBT was evaluated by ROC analysis. Results　With the exception of ACD, serum GDF15 level was significantly higher in each anemic subgroup than that in control group (all P<0.001). Median and range of serum GDF15 concentrations in hemolytic group (HA) were 2299 pg/ml and 444-13368 pg/ml respectively, which were greatly higher than that in iron deficiency anemia (IDA) and aplastic anemia (AA) (both P<0.001). Notably, GDF15 levels were remarkably elevated in SBT, with median and maximal concentrations being 7480 pg/ml and 13368 pg/ml, up to 28-fold and 50-fold increase respectively as compared to median concentration in control group, and were also significantly higher than that in non-SBT HA group (P<0.0001). Serum GDF15 levels were negatively correlated to Hb concentrations both in overall anemia and HA groups (with rank correlation coefficients of -0.4286 and -0.4903, and P <0.0001 and 0.0032 respectively). Similarly, serum GDF15 levels were positively correlated to all 4 types of reticulocyte indices in the overall anemia group. Nevertheless, no correlation could be documented in each anemia subgroup. As for the 48 cases of children with measurement of iron parameters, GDF15 levels were positively correlated to serum ferritin (SF), serum iron (SI) and transferrin saturation (TS), with P values of 0.0005, <0.0001 and <0.0001 respectively. While for 23 cases with hemolytic anemia who had iron investigation results, GDF15 was also positively correlated to SI and TS, with P values of 0.0009 and 0.0042 respectively. Finally, the precision of SBT diagnosis based on serum GDF15 determination was 93.7% -100% (95% confidence interval). With serum GDF15 concentration of 5000 pg/ml as the cutoff point, the specificity of SBT diagnosis was 98.5%. Conclusions　As expected, childhood β-thalassemia major in China is also characterized by remarkably elevated serum GDF15 levels, which might be intimately associated with marked bone marrow ineffective erythropoiesis. Determination of serum GDF15 is of great significance in the differential diagnosis of β-thalassemia major.