The study provides an account of the incidence of Haemoglobin E and α -thalassaemia mutations and interactions between these globin gene mutations with the help of haematological data analysis and molecular characterization among the tribes from North East India. The study deals with a large cohort of four hundred and thirteen tribal population consisting of 234 cases from Assam and 179 cases from Arunachal Pradesh, respectively. These cases were obtained during a random screening programme organized by Ramakrishna Mission (RKM) Seva Pratisthan, Kolkata in collaboration with RKM's North East Ashram for tribal populations of Dibrugarh in Assam and Itanagar in Arunachal Pradesh. These subjects from tribal populations attended the camp for routine clinical and hematological investigations. Clinical and haematological data were assessed in all 413 cases. Haemoglobin E, codon 26 (G → A) was found to be the most prevalent mutation in the population of Dibrugarh: 48 % (113/234) in Assam and Itanagar: 16 % (29/179) in Arunachal Pradesh. Eighty cases from Assam and thirty-two cases from Arunachal Pradesh were selected for molecular study of α thalassaemia mutations based on Hb <11 g/dl, MCV <78 fl and MCH <28 pg. While investigating α-thalassaemia, mutations we found a striking: 11 % (9/80) with two most common deletional α - thalassaemia mutations in a group of tribes consisting of mainly Ahom, Garo, Munda and unknown tribes in Assam. The interaction of α thalassaemia with homozygous HbE (HbE/HbE) was found in 4 Ahom and 1 unknown tribe. No such interaction was found among the Garo and other tribes. In Arunachal Pradesh-21.87 % (7/32) of the tribes were shown to have α globin gene defect but no interaction of α- thalassaemia mutations with Haemoglobin E has been noted there. This is the first report of the study of the two α-globin gene deletion mutations (-3.7 α and -4.2 α) and their interaction with Hb E among these tribes. It was found that presence of Hb E alone did not cause any significant clinical symptoms among the tribes of Assam and Arunachal Pradesh and its interaction with -3.7 and /or -4.2 alpha thalassaemia mutations did not have any significant effect on their clinical and hematological picture. The presence of several globin gene abnormalities in the tribes of North East India emphasizes high frequencies of thalassemia and haemoglobinopathies in these regions and needs serious attention to population studies, carrier identification and counselling to reduce the genetic burden among these tribes. © 2013 Archana Sharma Foundation of Calcutta.