In modern drug therapy adverse drug reactions are the common life threatening problem among patients causes morbidity and mortality. Involvement of HLA in drug hypersensensitivity well known underlying mechanism is unclear thus considered as thrust area for current research. Non nucleoside reverse transcriptase inhibitor Nevirapine (NVP) commonly used in HAART therapy. HLA-B07 alleles are highly polymorphic accounts 32% among Indian population and significantly associated with Nevirapine induced hypersensitivity. Insilico studies were used to dissect the molecular interaction of NVP with B alleles ability to alter the binding repertoire. Both conventional and non classical hydroden bonding occurrence between NVP and HLA confers the stable interaction within the binding cavity of HLA B pocket and F pockets which is meant for self peptides. Current study thus open up a new prospective of the HLA-associated NVP hypersensitivity which would be helpful in improving the drug safety in future.