Porous polymers carrying sulfonamide (SAM) groups with interconnected pores were prepared by high internal phase emulsion (HIPE) method. The resulting polymer named polyHIPE (PH) has the disadvantage of low surface area due to the large macropores. This disadvantage has been overcome through the hypercrosslinking reaction by introducing meso-and microporosities to the interconnected framework of hierarchically macroporous PH. The resulting hypercrosslinked polyHIPE (HCLPH) was successfully functionalized with chlorosulfonic acid and tris(hydroxymethyl)aminomethane (tris) in two consecutive steps to obtain a SAM-functionalized (SAM-f) polymer surface. It has been very well established that there is a selective interaction between the SAMs and human serum albumin (HSA). Here, we conduct an adsorption performance comparison study for a number of SAM-f-polymers, which differ from each other in the applied template strategy such as emulsion and suspension (PHs or beads) and/or the hypercrosslinking degree based on the reaction time of (0−5−15−60 min). SAM-f-15 min HCLPH with its unusual performance was found to achieve highly selective (compared to lysozyme and α-amylase) and very fast (80% of its uptake capacity in 2 min) adsorption of HSA. The polymer loaded with HSA can easily be regenerated by treating it with only tris buffer (pH 7) and was reused eight times without losing any significant adsorption capacity. The results of a comprehensive study of isotherms (Langmuir, Freundlich, Dubinin−Radushkevich) and kinetic (pseudo-first-order, pseudo-second-order, intraparticle diffusion) models as well as the thermodynamic analysis were presented for SAM-f-15 min HCLPH. The binding mechanism of HSA/SAM ligand complex was investigated by performing simplified molecular modeling via docking. Hydrophobic interactions and hydrogen bonding were found to be the major forces dominating the adsorption process. These results follow the outcome obtained from the thermodynamic analysis. The fast uptake, easy reuse protocol, and high affinity toward HSA make SAM-f-HCLPHs excellent materials for albumin adsorption.