This study was done on SD rat Sertoli-germ co-cultured cells (Sertoli-germ cells) with nickel nanoparticles (Ni NPs). A series of investigations were performed to observe the role of Ni NPs on the apoptosis of Sertoli-germ cells and to explore the long-chain non-coding RNA (lncRNA) functions on key signaling pathways and regulatory mechanisms. We found that Ni NPs had an apoptotic effect on Sertoli-germ cells. Ni NPs-induced apoptosis in Sertoli-germ cells involves the LOC102551356, Insulin-like growth factor-binding protein 3 (Igfbp3), and mitochondrial apoptosis pathway. The specific mechanism may be: during the process of Ni NPs-induced apoptosis in Sertoli-germ cells, the expression of LOC102551356 is up-regulated, and LOC102551356 activates the mitochondrial apoptosis pathway through targeted regulation of the target gene Igfbp3 in the P53-reduced apoptosis pathway. The results of this study will be important for the safety evaluation of Ni NPs in the future, and could provide an approach for the prevention or alleviation of the toxicity induced by Ni NPs.