<p>In this study, we thoroughly investigated the inhibitory effect of potassium sodium hydrogen citrate (PSHC) on renal calcium oxalate stones induced by glyoxylate in mice, explored the mechanism of action of PSHC in inhibiting calcium oxalate stone formation, and analyzed the therapeutic effect of PSHC in inhibiting calcium oxalate stone formation. Healthy SPF C57BL/6N male mice, which had not been exposed to any drugs, were randomly divided into four groups: Group A was the healthy group; group B was the stone group; group C was the PSHC gavage group; and group D was the PSHC intraperitoneal injection group, and consecutively modeled and administered for 7&#xa0;days, after which, the kidneys, blood, and urine of the mice in each group were collected. No calcium oxalate crystals were observed in group A, calcium oxalate crystals were observed in group B, no calcium oxalate crystals were observed in group C, and calcium oxalate crystals were observed in group D. Nanocrystals in urine were observed; group B had a more aggregated distribution and sharper morphology than group A. Groups C and D had a more dispersed distribution and rounder morphology than group B.&#xa0;The results show that PSHC can inhibit calcium oxalate stone formation by lowering urinary oxalate, reducing reactive oxygen species production and oxidative stress in modelled mice, and also inhibit calcium oxalate stone formation by elevating urinary citrate to inhibit the binding of calcium oxalate crystals to cell membranes. Furthermore, PSHC prevents nanocrystal aggregation and growth, thereby reducing calcium oxalate stone formation.</p>