A new polymeric laponite nanoclay heterogeneous catalytic system based on HPMC (hydroxypropyl methyl cellulose) was developed for direct Mannich-type reaction of ketones with substituted benzaldehydes and anilines to afford corresponding beta-amino ketones in good to high yields. Interestingly, cyclic ketones exhibited different chemoselectivity. Cyclopentanone underwent aldol condensation to give crossed-aldol product, while cyclohexanone and cyclopentanone afforded corresponding Mannich adducts. In the case of cyclohexanone, stereoselectivity was changed depending on the nature of the substitution on benzaldehydes, in which, moderate electron-donating and electron-withdrawing groups afforded the anti isomer as major products, but strongly electron-donating substituted benzaldehydes led to syn isomer as the major Mannich adducts. Mannich reaction with cycloheptanone led to Mannich adducts with excellent syn selectivity.