Objective To detect the differential expression of osteopontin (OPN)-related long non-coding RNAs (lncRNAs) in sodium oxalate crystallization-induced renal tubular epithelial cell injury and to explore the role of OPN-related lncRNAs in the pathogenesis of renal injury by crystallization. Methods The renal tubular epithelial cells (HK-2 cells) were cultured and stimulated with 20 mmol/L sodium oxalate to establish the renal injury cells model. The OPN knockdown in HK-2 cell injury was carried out by transfecting OPN small interfere RNA (siRNA) into the cells, which was set up as the OPN-siRNA group; the cells in control group (NC-siRNA group) were transfected with negative random control sequences. The lncRNAs and mRNAs differential expressions were screened and identified by Arraystar Human lncRNA V4.0 Microarray in two groups, and the microarray results were analyzed by bioinformatics methods. Results Human genome lncRNA microarray results showed there were a total of 583 differentially expressed OPN-related lncRNAs in renal injury cell model of renal tubular epithelial cell induced by sodium oxalate crystallization, including 354 up-regulated lncRNAs and 229 down-regulated lncRNAs in OPN-siRNA group; there were a total of 235 mRNAs with differential expression, including 139 up-regulated mRNAs and 96 down-regulated mRNAs. Bioinformatics analysis results showed the differentially expressed lncRNAs were correlated with cell growth, enzyme activity regulation and other biological processes. Conclusion OPN-related differentially expressed lncRNAs are involved in the mechanism of the sodium oxalate crystallization-induced HK-2 cell injury.