We report high-pressure structural studies (52 GPa) at room temperature combined with magnetic [(M(T):1GPa] and electrical resistivity [(ρ(T):0-21GPa)] measurements down to 2 K on Fe0.99Ni0.01Se0.5Te0.5 superconductor using designer diamond anvils (D-DAC) pressure cell. The M(T) data show huge enhancement of superconducting transition temperature (Tc) from 8.62 to 14.8 K (1 GPa) and ρ(T) reveal maximum enhancement of Tc ~ 30.5 K at 3 GPa (dTc/dP = ~ 7.19 K/GPa) followed by moderate decrease of Tc up to 19 K at 7.5 GPa, and further increasing pressure Tc gets vanished at 10.6 GPa. The reduction of Tc due to the occurrence of structural transition that is likely associated with possible reduction of charge carriers in the density of states in Fermi surface. The high-pressure XRD measurement shows tetragonal phase exists up to 7 GPa, followed by mixed phase which is visible between 7.5 GPa and 14.5 GPa. The structural transformation occurs at 15 GPa from tetragonal (P4/nmm) to NiAs -type hexagonal phase (P63/mmc) and it is stable up to 52 GPa, confirmed from the equation of state (EOS) and it can be correlated with variation of Tc under pressure for Fe0.99Ni0.01Se0.5Te0.5 chalcogenide superconductors.