Research efforts towards developing near-infrared (NIR) therapeutics to activate the proliferation of human keratinocytes and collagen synthesis in the skin microenvironment have been minimal, and the subject has not been fully explored. Herein, we describe the novel synthesis Ag₂S nanoparticles (NPs) by using a sonochemical method and reveal the effects of NIR irradiation on the enhancement of the production of collagen through NIR-emitting Ag₂S NPs. We also synthesized Li-doped Ag₂S NPs that exhibited significantly increased emission intensity because of their enhanced absorption ability in the UV–NIR region. Both Ag₂S and Li-doped Ag₂S NPs activated the proliferation of HaCaT (human keratinocyte) and HDF (human dermal fibroblast) cells with no effect on cell morphology. While Ag₂S NPs upregulated TIMP1 by only twofold in HaCaT cells and TGF-β1 by only fourfold in HDF cells, Li-doped Ag₂S NPs upregulated TGF-β1 by tenfold, TIMP1 by 26-fold, and COL1A1 by 18-fold in HaCaT cells and upregulated TGF-β1 by fivefold and COL1A1 by fourfold in HDF cells. Furthermore, Ag₂S NPs activated TGF-β1 signaling by increasing the phosphorylation of Smad2 and Smad3. The degree of activation was notably higher in cells treated with Li-doped Ag₂S NPs, mainly caused by the higher PL intensity from Li-doped Ag₂S NPs. Ag₂S NPs NIR activates cell proliferation and collagen synthesis in skin keratinocytes and HDF cells, which can be applied to clinical light therapy and the development of anti-wrinkle agents for cosmetics.