9-Anthracenecarboxylic acid (9-Ac) was reported early as a chloride channel inhibitor and was found to exhibit significant anti-proliferative activity on leukemic cells, but has not been researched in solid tumor cells. Herein, a 9-anthraceneic acid derivative was introduced into the cyclometalated Iridium (III) species to construct a novel Iridium (Ir) complex Ir-9-Ac, Ir(ppy)2(9-Ac-L)PF6 (ppy = 2-phenylpyridine, 9-Ac-L = N-((4′-methyl-2,2′-bipyridin-4-yl)methyl)anthracene-9-carboxamide), which could accumulated in lysosomes. Ir-9-Ac showed good cytotoxic activity against several tumor cell lines, notably on A549 cells. Besides Ir-9-Ac could inhibit the cell colony formation and growth of the 3D cell spheroids, demonstrating the potential to suppress tumors in vivo. This design provided a platform for the design of cyclometalated Iridium (III) anticancer complexes. Ir-9-Ac, Ir(ppy)2(9-Ac-L)PF6 (ppy = 2-phenylpyridine, 9-Ac-L = N-((4′-methyl-2,2′-bipyridin-4-yl)methyl)anthracene-9-carboxamide) exhibited higher activity against solid tumors lines, especially towards A549 cell lines. It was accumulated in the lysosome, and induced cell cycle arrested in phase G0/G1, inhibited the colony formation and activated the endogenous apoptosis genes by an ROS-dependent activation of p38 occurs in response to lysosomal damage. Display omitted •A metal complex based on nontoxic 9-anthraceneic acid (9-Ac) exerting anti-solid tumor cell effects.•Ir-9-Ac (Ir(ppy)2(9-Ac-L)PF6) is primarily accumulated in the lysosome of A549 cells.•Ir-9-Ac inhibits 3D multicellular tumor spheroids model mimicking the tissue microenvironment.•Ir-9-Ac enhances lysosome damage by a reactive oxygen species-dependent activation of p38 pathway.•Ir-9-Ac induces the endogenous apoptosis in response to lysosomal damage.