The current lubricating artificial tear ingredient for dry eye disease (DED) therapy, i.e., sodium hyaluronate (SH), is ineffective because it is difficult to stay on the ocular surface long term. To address this problem, we developed an injectable in situ lubricative copolymer that can firmly adhere to the ocular surface for long-lasting in situ lubrication. Lubrication was achieved by the zwitterionic monomer [2-((methacryloyl)oxy)ethyl]phosphorylcholine (MPC) with hydration lubrication property. Meanwhile, in situ adhesion performance was achieved by the reactive ester monomer N-hydroxysuccinimidyl acrylate (AA-NHS), which is capable of amide bonding reactions to the tissue surface. The optimum feeding ratio of MPC versus AA-NHS for free radical polymerization was confirmed by friction tests, and this group was named MPC-co-AA-NHS (MAN). We established a BALB/c mice DED model to verify its biofunctionality in vivo. The results showed that MAN is a promising in situ lubrication material that effectively relieves DED.