Screening toxic-element-free and biocompatible electrochemiluminophores was crucial for electrochemiluminescence (ECL) evolution. Herein, l-glutathione (GSH)-capped Ag-Ga-In-S (AGIS) nanocrystals (NCs) were prepared by doping Ag-In-S (AIS) NCs in a doping-in-growth way and utilized as a model for both ECL modulating and developing multinary NC-based electrochemiluminophores with enhanced ECL performance than trinary NCs. AGIS NCs not only primarily preserved the morphology, size, phase structure, and water monodisperse characteristics of AIS NCs with broadened band gap but also demonstrated obviously enhanced oxidative-reduction ECL than AIS NCs. Importantly, ECL of AGIS NCs was located at the near-infrared region with a maximum emission wavelength of 744 nm and could be utilized for an ECL immunoassay with human prostate-specific antigen (PSA) as a model, which exhibited a linearity range from 0.05 pg/mL to 1.0 ng/mL and a low limit of detection of 0.01 pg/mL (S/N = 3). This work provided a promising alternative to the traditional binary NCs for developing toxic-element-free and biocompatible electrochemiluminophores with efficient near-infrared ECL.