The sixth most common cancer in the world, esophageal cancer, requires aggressive treatment such as surgery, chemotherapy, radiotherapy, and immunotherapy. Phytochemicals and medicinal plants are being used in the green synthesis of nanoparticles. Our study aimed to synthesize ZnO-SnO2 nerolidol nanocomposite and study its effects on esophageal squamous cell carcinoma cells. UV spectroscopy showed significant absorbance at 288 nm, transmission electron microscopy and DLS showed spherical shapes, and transmission electron microscopy also showed 108 nm average diameters. The ZnO-SnO2 nerolidol nanocomposite was also investigated using energy-dispersive X-ray analysis, Fourier transform infrared spectroscopy, photoluminescence, and field emission scanning electron microscopy. A cytotoxic effect was observed against KYSE-150 cells with an IC50 concentration of 14.9 mu g/mL. The ZnO-SnO2 nerolidol nanocomposite inhibited cancer cell proliferation in KYSE-150 cells and enhanced apoptosis by altering its mitochondrial membrane potential. The ZnO-SnO(2 )nerolidol nanocomposite also enhanced oxidative stress, leading to a decrease in superoxide dismutase, catalase, and glutathione and an increase in lipid peroxidation. Ultimately, ZnO-SnO2 nerolidol nanocomposite enhanced the caspase cascade by inducing caspases 3, 8, and 9 in KYSE-150 cells. On the whole, we suggest that the ZnO-SnO2 nerolidol nanocomposite can be an effective treatment strategy against esophageal squamous cell carcinoma in KYSE-150 cells. However, understanding molecular circuits is still warranted.