Introduction: The large clinical spectrum of haemoglobin E-beta (HbE/β) thalassaemia leads to the investigation of complex mechanisms involved in erythropoiesis. DNA methylation in LARP2 is one of the potential epigenetic mod- ifiers not fully explored in HbE/β and β-thalassaemia major. This study aimed to analyse DNA methylation profile and gene expression of LARP2 using peripheral blood (PB) in nucleated red blood cells (NRBCs) for the source of DNA of HbE/β- and β-thalassaemia major patients. Methods: PB were collected from 33 transfusion-dependent thalassemia patients from Hospital USM and Hospital RPZII, Kelantan, Malaysia. DNA methylation profile and gene expression of LARP2 were examined by bisulphite sequencing PCR and quantitative real-time PCR respectively. Results: Par- tial DNA methylation of LARP2 was observed in 43% (9/21) HbE/β- and 17% (2/12) β-thalassaemia major patients. LARP2 expression (1.49±26.60) in HbE/β-thalassaemia was not significant against normal controls and β-thalassae- mia major (p>0.05). In contrast, LARP2 expression (6.8±16.42) in β-thalassaemia major showed a significant up-reg- ulation against normal controls (p