Display omitted •Intercalated molecules of OCP could be exchanged by PO4 during phase conversion.・The formed HPO4-OH layer structure is unstable, then, easily convert.•PO4 in buffer solution accelerated phase conversion process of OCP to HAp.•During this process, crystals morphology was no obvious changes. Octacalcium phosphate (OCP) is a layered calcium phosphate compound that has attracted significant attention as a new biomaterial due to its excellent biocompatibility. Its interlayer structure, known as HPO4-OH layer, can be easily replaced by dicarboxylic acid. However, the kinetical ionic and/or molecular exchange process of substituted dicarboxylic acid into OCP interlayer is still unclear. Therefore, in this study, we evaluate the molecular exchange process for thiomalate (SH-malate)-substituted OCP (OCP-SH-malate) during the phase conversion process to other phases in disodium hydrogen phosphate solution (Na2HPO4). When the OCP-SH-malate is immersed in 1 mol/L Na2HPO4 at 40 °C while shaking at 200 rpm, SH-malate, first desorbed from the interlayer of OCP-SH-malate and the HPO4-OH layer structure, is formed at the interlayer where the SH-malate was dissolved. The HPO4-OH layer structure is unstable, making it easily convert to hydroxyapatite (HAp) via dehydration upon further immersion. During this reaction, besides the dissolution of marginal edges of the crystals, crystals morphology was no obvious changes, neither were there evidences of dissolution and collapsing of OCP crystals nor nucleation of newly created crystals.