A fundamental chemoselectivity challenge that remains intrinsically unsolved in aldol-type reactions is the suppression of self-aldol reactions with enolizable aldehydes in reactions such as cross-aldol processes. Contrasting with the usual practice of using large excesses of one component to compete with the undesired self-aldehyde condensation reactions, we have developed an enzyme-like polymer catalyst consisting of a hyperbranched polyethyleneimine derivative and proline that can eliminate the self-aldol reactions by suppressing an irreversible aldol condensation pathway. Control experiments and preliminary mechanistic studies suggest that the polymer catalyst provides an optimum environment for the aldol reaction to proceed selectively in water, and the catalytic conditions provided by the polymer are difficult to duplicate with typical small molecule analogues. This polymer catalyst system or its modified version has potential applications in developing a new or more efficient synthesis, as demonstrated in a dynamic catalytic process for the preparation of a,p-unsaturated ketones using cross ketone/aldehyde reactions without the need for excess substrates.