Radiotherapy is one of the main therapeutic methods for cancers; however, nonselective killing of normal cells and tumor cells by X-ray inevitably results in toxicity and side effects. Developing low-toxicity and high-efficiency radiosensitizers to reduce the practical dose of X-ray is a promising approach to overcoming these side effects. Here, we report the use of carboxylate-containing organic ligands to construct one-dimensional high-Z lanthanide chains for efficient response to X-ray. The one-dimensional lanthanide chains are stacked through weak interactions to form coordination nanoframeworks in the presence of polyethylenimine (PEI). The morphology and activity of the synthesized nanoframeworks can be regulated through selenium atom engineering. This study presents a promising approach for effective radiotherapy through selenium-engineering stable lanthanide nanoframeworks with precise coordination structures as radiosensitizers to mitigate X-ray side effects.