Cancer is the second leading cause of death worldwide. Small-molecule anticancer agents with tolerable safety profiles have been developed to improve survival rates. Indazole analogues have received considerable attention due to their anticancer properties. A series of N3-acyl-N5-pyrimidinyl-3,5-diaminoindazoles were synthesized and their antiproliferative activities were evaluated in Caki, A549, HepG2, AMC-HN4, and SNU484 human cancer cell lines. Cellular selectivity of 3,5-diaminoindazole with a modified structure of the N5-pyrimidinyl substituent was studied. While both compounds 9a and 9b showed a high selectivity for the HepG2 cell line, compound 9b had a higher selectivity than 9a, with an IC50«0.1 μM.