Abstract The development of stable carrageenan nanoparticles connected to the sulfate functional group of carrageenan and barium ion for the use of selectively targeting cancer cell and imaging contrast to help with diagnosis (tracing/imaging) is the concern of the present research. This study provides an overview of ion substitution chemistry, highlighting the role of ions and how they affect the applicability of carrageenan. The characteristic of barium sulfate, which is widely used as radiopaque to provide contrast for diagnostic radiographic examinations in the gastrointestinal mucosa, is provided by its linkage with the barium ion despite K⁺’s natural binding with carrageenan. The additional role of the Ba ion linked carrageenan was found highly selective for cancer cell through the in vitro cell line assay; however, the nonattachability to the normal cell makes useful to trace and treat the cancer cell. The tracing is possible because of the barium sulfate functional group and its nanosize molecule, which shows precision medicine, fluorescence, and X-ray/CT imaging character, to be utilized as the diagnostic purpose, especially to tumor cell. The apoptosis from the Ba²⁺ ion by the inhibition of outflux of K⁺ to disturb the osmosis of cell and selectivity of the molecules because of high pKa (Logarithms of acid dissociation constant) value, which makes the drug more active anionic (nonpolar) form in the cancer cell and ionic form (polar) in the normal cell, which avoids the interaction with normal cell and facilitate the interaction with cancer cell. In conclusion, the cancer cell selectivity with fluorescence and radiopaque properties of Ba ion linked carrageenan makes the molecule useful for tracing, imaging, and treating cancer cell with high selectivity.