Ultrahigh-molecular-weight polyethylene (UHMWPE) stands out as a popular artificial joint material. However, wear limits its service life, which is mainly caused by accumulation of plastic deformation. The plastic deformation on the frictional interface reflects the early wear of UHMWPE. To investigate the effect of squalene, a typical component in the body fluid, on the tribological properties of UHMWPE at microscopic scale, the diffusion behavior of squalene into polyethylene and its influence on the plastic deformation of polyethylene are discussed using the molecular dynamics (MD) simulation. The lubrication model shows that polyethylene reconstructed from the interface to lower substrate, with refactor gaps between polyethylene chains. This promotes squalene molecules to gradually diffuse into polyethylene from these gaps and causes the polyethylene structure to become loose. On the other hand, in the diffused model, squalene in polyethylene substrates increases the plastic deformation of polyethylene. The separation of squalene reduces the interaction strength between adjacent polyethylene chains and accelerates the disentanglement of polyethylene. The flexibility of “C═C” bonds in squalene allows the continuous adjustment of its spatial structures to adapt the space between polyethylene chains. The squalene fragments will not hinder the plastic flow of polyethylene.