A series of novel 10-substituted camptothecin analogs (3-10) with a carbamate linker were synthesized, and their biological activities were evaluated. The amino acid-linked carbamate derivatives (8-10) of the camptothecin-type natural product not only possessed good to excellent inhibitory activity against three human tumor cell lines K562, HepG2, and HT-29, but also showed significantly less cytotoxicity against normal human cell HEK293 (half maximal inhibiting concentration >10 μM). The selectivity of compound 9 toward tumor cells relative to normal cells is at least 250 times better than that of camptothecin. The preliminary testing result indicated that the solubility of these compounds was also improved compared to that of 10-hydroxy camptothecin.