Conventional molecular dynamics (cMD) simulations were conducted to investigate the behavior of Burkholderia cepacia lipase (BCL) in phosphonium-based ionic liquid (PhIL) aqueous solutions. The results revealed that PhILs influence BCL conformational dynamics, particularly lid opening, which modulates enzyme activity while maintaining the active site region's shape. Hydrogen bond (HB) analysis indicated that PhILs altered HBs in the catalytic triad, especially between Ser87 and His286, though this did not appear to be the primary driver of activity changes. Minimal enzyme-anion HBs in [Cl]- and [Br]-based PhILs were associated with reduced structural stability and the lowest activities, whereas [NTf2]-based PhIL, with balanced enzyme-water and enzyme-anion HBs, fostered optimal enzyme conformations and the highest activity. Increased solvent-accessible surface area (SASA) in PhILs compared to water was linked to lid movement and changes in active site entrance size. Clustering analysis revealed that the α5 helix loses its conformation in water but retains its structure in [P666(14)][NTf2], highlighting the IL's stabilizing effect and preservation of key secondary structures. Radial Distribution Function (RDF) analysis showed that cations with longer alkyl chains block the active site entrance in phosphonium chloride ILs, reducing activity, whereas non-halogen anions enhance active site accessibility, explaining the improved activity in [P666(14)][Phosp] and [P666(14)][NTf2]. These findings provide valuable insights into the molecular mechanisms underlying PhIL-BCL interactions and their impact on enzyme activity.