The escalating contamination by per- and polyfluoroalkyl substances (PFAS) has become an urgent issue in recent years, and the structural diversity of PFAS is the major challenge for effective pollution control. Herein, we take the intrinsic advantages of squaramide and prepare a new two-dimensional covalent organic framework (FSQ-1) that exhibits broad-spectrum PFAS affinity. The tailor-made linker forges hydrogen-bond donors, hydrogen-bond acceptors, and fluorophilic segments into one framework. The obtained material exhibits multipoint and multitype affinity to PFAS with different structures, by which high-efficient and broad-spectrum removal of various PFAS can be simultaneously achieved. Notably, the thermodynamic profiles provided by isothermal titration calorimetry (ITC) experiments further illustrate the underlying mechanism of the broad-spectrum affinity. FSQ-1 can also be applied for efficient PFAS extraction in trace-level PFAS analysis.