OBJECTIVE： To study the effects of tetracycline on the expression of calcium-sensing receptor （CaSR） and Claudin-14 in nanobacteria-infected （NB） human renal tubular epithelial cells HK-2， and to provide reference for inhibiting the formation of kidney stone. METHODS： HK-2 cells were divided into blank control group， NB group and tetracycline group （NB+tetracycline）， with 3 complex holes in each group. They were given relevant nanobacteria and drug for 24 h. Morphology and ultrastructural changes of cells were observed by TEM. mRNA and protein expression of CaSR and Claudin-14 were measured by real-time quantitative PCR （qRT-PCR） and Western blot assay. RESULTS： Compared with blank control group， the damaged structure of cell membrane， exposed nucleus， disappeared microvilli， small number of mitochondria and swollen structure were found in NB group； mRNA and protein expression of CaSR and Claudin-14 were increased significantly （P＜0.05）. The complete structure of cell membrane， disordered structure of microvilli， disappeared local villi and not obvious swollen of some mitochondrial structure were found in tetracycline group； mRNA and protein expression of CaSR and Claudin-14 were increased significantly （P＜0.05）. Compared with NB group， mRNA and protein expression of CaSR and Claudin-14 were decreased significantly in tetracycline group （P＜0.05）. CONCLUSIONS： NB may improve the formation of kidney stones by up-regulating the mRNA and protein expression of CaSR and Claudin-14 in HK-2 cells， while tetracycline may reduce the mRNA and protein expression of CaSR and Claudin-14 by anti-NB effect so as to inhibit kidney stone formation.