Objective Cyclosporine A (CsA), a calcineurin inhibitor, has improved allograft survival in solid organ transplantation and was also demonstrated that CsA induces autophagy, both in vitro in human tubular cells and in vivo in mouse kidneys, and that autophagy serves as a protective mechanism against CsA toxicity, showing that CsA-induced autophagy is triggered by endoplasmic reticulum (ER) stress. In this study, the presence of BI-1 induces autophagy in CsA-induced kidney damage through the lysosomal activation (ERAD II). Methods The experiment was performed in cell line and animal models. We used primary BI-1+/+ and BI-1-/- mouse proximal tubular cell. GFP-LC3 transgenic mice were obtained from RIKEN bio resource center Japan. The studies carried in cell line and mice are western blot analysis, electron microscopy, immunohistochemistry, real time PCR. Results The CsA-induced autophagy is more highly stimulated in BI-1-overexpressing cells, which is also regulated by bafilomycin, meaning the role of lysosome on BI-1 cells. Through in vivo approach, the CsA-induced autophagosome and vesicle formation are also increased, relating with the protective function of BI-1 on CsA-induced nephrotoxicity. Conclusion Bax inhibitor 1 as a protective role in human renal tubular cells under ER stress conditions protect against CsA toxicity by formation of autophagosome.