A novel ICP MS DNA assay based on lanthanide labels and hybridization chain reaction amplification has been developed. This approach utilizes an enzyme-free amplification and can be operated under mild conditions. The developed assay exhibits desirable sensitivity and is suitable for multiple DNA target analysis because a general DNA hybridization approach is applied to capture target DNA. Considering lanthanide labels and ICP-MS have excellent ability in high-level multiplexing analysis, this approach holds great potential for practical use in quantitative determination of DNA targets for future clinical applications.