AbstractWith the rapid growth of modern information data, DNA has emerged as a novel medium for data storage due to its durability, replicability, sustainability, and high density. This study focuses on the compatibility, high capacity, and random access of DNA data storage systems. A calcium phosphate (CaP) mineralized fluorescent SiO2 DNA (FSD@CaP) microspheres is developed by encapsulating fluorescence‐labeled encoding DNA files onto the surface of the SiO2 microspheres that are intrinsically sized and fluorescent as addressed two‐dimensional (2D) barcodes. The various sizes of SiO2 and various fluorescence‐labeled encoding DNA files forming 2D barcodes of FSD@CaP. The 2D barcodes enhance the system's compatibility while allowing multiplexed random access to DNA files. The high‐capacity DNA storage permits effective single access to the DNA file using a minimal number of FSD@CaP microspheres, without impacting the matrix of the system. Ultimately, random access to arbitrary DNA files within a complex pool of distinct 2D barcode‐tagged FSD@CaP microspheres is demonstrated by utilizing a flow cytometer for multiplexed sorting. Consequently, the strategy of this storage system provides a scalable concept for compatibility and multiplexed random access to DNA data sets.