Two types of thiazole derivatives are synthesized through a multistep cascade sequence with Pd-metalated phosphorus-doped porous organic polymers (POPs) as heterogeneous catalysts. The POPs could be used as both ligands and catalyst supports. No obvious aggregation and loss of any catalytic activity of the catalysts were observed after 10 runs of the reaction. More importantly, imidazo[4,5- d]thiazoles, which are a new class of thiazole derivatives, could be obtained through K2CO3-promoted intramolecular cyclization of the synthesized polysubstituted thiazoles. Furthermore, the in vitro anticancer activity of these new compounds were tested with MTT assay, and compound 4b exhibited good antitumor activity toward T-24 and A549 cells with IC50 values of 10.3 ± 0.8 and 11.8 ± 0.5 μM, respectively. In addition, the action mechanism of 4b on tumor cells was determined.