Traditional adhesives with strong adhesion are widely applied in the fields of wood, building, and electronics. However, the synthesis and usage of commercial adhesives are not eco-friendly, which are harmful to human health and to the environment. In this study, a green cellulose nanofibrils/poly(hydroxyethyl methacrylate- co -dopamine methacrylamide) (CNFs/P(HEMA- co -DMA)) adhesive with excellent biocompatibility and strong bonding strength has been fabricated. P(HEMA- co -DMA) with a catechol content of 7.1 mol % was synthesized using dopamine methacrylamide and hydroxyethyl methacrylate. The CNFs/P(HEMA- co -DMA) adhesive was generated by cross-linking P(HEMA- co -DMA) solution using cellulose nanofibrils (CNFs). Strong adhesion was realized on various substrates, with a maximum lap shear strength of 5.50 MPa on steel. The NIH 3T3 cells test demonstrated that the adhesive possessed excellent biocompatibility. The green catechol-containing CNFs-cross-linked adhesive has promising potential for applications in medicine, electronic, food packaging, and engineering.