Polo like kinase 4 (PLK4) is a critical member of the polo-like kinase family that works as a master regulator of centriole duplication and mitotic progression. Overexpression of PLK4 has been documented in various cancers and PLK4 inhibitors are regarded as a potential strategy for cancer treatment. In this study, we identified indazole derivative 8 as a hit compound through a virtual screening approach. Subsequent fragment-based rational drug design strategy was used to modify the chemical structure of compound 8 and yielded 34 indazole derivatives targeting PLK4. Among them, compound 34b (CZL-S092) exhibited a potent PLK4 inhibitory activity with an IC value of 0.9 nM, and exceptional selectivity in a panel of 37 kinases. At the cellular level, compound 34b demonstrated significant antiproliferative activity against the neuroblastoma cell lines IMR-32 and SH-SY5Y with IC values of 1.143 μM and 1.329 μM, respectively. Moreover, the colony formation, flow cytometry, wound healing and immunofluorescence analysis further confirmed the in vitro antitumor effects of compound 34b. Meanwhile, compound 34b displayed excellent in vitro drug permeability and plasma protein binding. Furthermore, compound 34b exhibited acceptable in vivo pharmacokinetic properties with the oral bioavailability of 22.1 %. Overall, compound 34b exhibited potent anti-neuroblastoma activities and acceptable pharmacokinetic properties, which served as a favorable lead compound targeting PLK4.