This study introduces a therapeutic strategy that simultaneously addresses four fundamental challenges in oncology: efficacy, safety, the emergence of drug resistance, and pan-cancer applicability. We demonstrate that aurintricarboxylic acid (ATCA) suppresses malignant phenotypes across a diverse range of cancers by targeting the hyperactive translation initiation machinery, a universal hallmark of cancer. This core mechanism underpins its validated efficacy in lung, breast, colorectal, and liver carcinomas, while its unique action of disrupting ribosome assembly without stalling them underlies its exceptional safety profile and formidable barrier to resistance. The significance of our work is underscored by several key findings: