Anemia is a global health problem that occurs both in developed and developing countries. About 1.2 million people in the world are affected with Anemia, especially iron deficient (ID). Iron refractory iron deficiency anemia (IRIDA) is one of genetic recessive, characterized by refractory anemia from oral iron therapy but partially responsive to parenteral therapy. A transmembrane protease serine 6 (TMPRSS6) is a gene providing hepcidin suppression and is a regular iron metabolism. This gene allows for the compensatory mechanism of iron absorption. Hemoglobin has an association with TMPRSS6 which detected at a low level and it’s may be due to an iron imbalance of homeostasis. On the other hand, polymorphism of the SNP gen TMPRSS6 rs855791 and rs4820268 also iron intake had an association both with the iron status, particularly in Serum Ferritin (SF) concentration. TMPRSS6 is encoding a Matriptase-2 which plays an essential role in hepcidin. Down-regulation of hepcidin levels is associated with matriptase-2, which means a regulator key for iron hemostasis. A mutation in TMPRSS6 pathogenically may uninhibit the hepcidin production, causing IRIDA. Soluble transferrin receptor (sTfR) is also associated with the TMPRSS6 gene which is caused by fractional iron absorption as one of many factors induced by IRIDA. TMPRSS6 has an important role in IRIDA condition. A mutation may affect the hepcidin levels and lead to iron deficiency. Hepcidin levels together with hemoglobin, serum ferritin and sTfR affected by this TMPRSS6 gene mutation. SNPs of TMPRSS6 also has a different role in IRIDA. Although, it is very limited information about this gene and its association with IRIDA, further research in larger population with including races and ethnics are needed