Heavy-metal-free silver based I-III-VI semiconductor nanocrystals (NCs), including ternary silver indium sulfide (AgInS₂) and derivative quaternary silver indium zinc sulfide (i.e., AgInZn₂S₄) NCs, possess advantages of low toxicity, and size-tunable band gaps approaching near-infrared spectral range, which make them candidates for use in optoelectronic and biological devices. Herein, we report syntheses of AgInS₂ based NCs starting from In₂S₃ template, which have been performed both in organic and aqueous phase through cation exchange. As a result, ternary silver indium sulfide and quaternary silver indium zinc sulfide NCs are obtained in both organic and aqueous media, and confirmed to be orthorhombic AgInS₂ NCs and hexagonal AgInZn₂S₄ NCs, respectively. Furthermore, the aqueous AgInZn₂S₄ NCs with red emission and low cytotoxicity are explored for the cancer cell imaging.