We recently reported that fibronectin (FN: 230 kDa) was oversecreted from the renal tubular cells as a result of the stimulation of COM crystals, and inhibited the adhesion of COM crystals to renal tubular cells. In the study presented here, we investigated whether FN can prevent injury to renal tubular cells caused by oxalate and COM crystals and tried to identify the relation with inhibition of crystal adhesion. The protective effect of FN against renal tubular cell injury by exposure to oxalate and COM crystals was examined by measuring the lactate dehydrogenase (LDH) activity and using a non-radioactive proliferation assay. Moreover, crystal-cell interaction was morphologically assessed by means of scanning electron microscopy (SEM). LDH was reduced significantly by the addition of FN in a dose-dependent manner. Cell viability increased significantly with the addition of FN, also in a dose-dependent manner. Moreover, the morphological SEM study showed that few crystals were attached to the surface of cells when FN was added compared to the number of adhering crystals when FN was not added. FN was found to have an inhibitory effect on renal tubular cell injury caused by exposure to oxalate and COM crystals. We speculate that the inhibitory effect of FN on the adhesion of COM crystals is related to the inhibitory effect of exposure to COM crystals on renal tubular cell injury.