Malaria is a most causative agent for worldwide death. Plasmodium falciperum infected malaria most dangerous than other plasmodium species. It has closely association to compliment receptor type -1 (CD35) gene polymorphism. CD35 (CR1) is a cell surface receptor for plasmodium falciperum containing PfEMP-1 as a legend. Density of CD35 on erythrocyte can be determined by CR1 allele (HH, HL, and LL). HH allele of CR1 gene express high density of CD35 whereas LL in low density. High density of CD35 is more susceptible to falciperum infection. CD35 is also responsible for sever malaria. During plasmodium infection, pro-inflammatory cytokine like TNF-α, IFN-γ levels are increased. The elevated ratio of TNF-α/IL10 indicates falciperum infection. Cell adhesion protein like VCAM, ICAM also mediate the malarial infection.