Host resistance against parasitic infestation is quite important to study in current days, since till date no effective vaccines against parasites have been developed. Moreover, indiscrimate use of regular deworming as a practice may lead to the development of resistance to antihelmiths (as in case of antibiotic resistance against bacteria) or development of antihelminth resistant strains among dreadly parasites. In this present study, we attempt to explore immune response gene againstHaemonchus contortusas dreadly parasite against sheep model. In our lab, we have already detected some of such promising genes, namely RIGI (earlier known antiviral in action), CD14, IL6 and IL10 (earlier known antibacterial in action). In this current publication, we have explored the role of MyD88 in mediating resistance against parasitic infestation. We have characterized ovine MyD88 molecule, identified important domain, analyzed molecular docking, identified the binding site withH. contortusthroughin silicostudies, network and pathway analysis, followed by differential mRNA expression profiling, ultimate confirmation through immunohistochemistry. Identification of immune response genes against parasites may lead to immunomodulation, genomic selection, gene therapy or even development of disease resistant stock of sheep through gene editing approach.