The study aimed to explore the effect of the nuclear factor-kappa B signaling pathway on apoptosis of rat renal tubular epithelial cells caused by calcium oxalate monohydrate crystals. After being cultivated in vitro, NRK-52E cells were split into a control group, 1 mm calcium oxalate monohydrate group and 10 μM QNZ+1 mm calcium oxalate monohydrate group. The optical density value was detected via cell counting kit-8 assay, the content of lactate dehydrogenase in cell supernatant was detected via colorimetry, and the expressions of nuclear factor-kappa B signaling pathway-related proteins p65 and p50 and B cell lymphoma-2, tumor necrosis factor receptor 1 and caspase-3 were determined through Western blotting. 1 mm calcium oxalate monohydrate could significantly reduce the proliferation ability of NRK-52E cell and cause cytotoxicity. 1 mm calcium oxalate monohydrate significantly up-regulated the expressions of p65, p50, tumor necrosis factor receptor 1 and caspase-3, and significantly lowered the B cell lymphoma-2. Besides, 10 μM QNZ+1 mm calcium oxalate monohydrate obviously down-regulated the expressions of p65, p50, tumor necrosis factor receptor 1 and caspase-3, and obviously increased the B cell lymphoma. The apoptosis of rat renal tubular epithelial cells in rats with calcium oxalate kidney stones may be promoted through activating the nuclear factor-kappa B signaling pathway. Inhibiting the nuclear factor-kappa B activity can alleviate apoptosis and improve renal cell function.