Backgrounds Kidney renal clear cell carcinoma (KIRC) is a major pathological type of renal cell carcinoma (RCC), and the prognosis of advanced KIRC patients is often unsatisfactory. Some lysine oxidase (LOX) family genes have been proven to be upregulated in some malignancies and play pivotal roles in the carcinogenesis. However, their roles in KIRC remain unclear. Materials and Methods Here, we used some online databases (eg, ONCOMINE, GEPIA, UALCAN, c-BioPortal, Human Protein Altas) to comprehensively explored the expression levels and the prognostic values of LOX family genes in KIRC using bioinformatic methods. Results The results revealed that lysyl oxidase (LOX) and lysyl oxidase-like 2 (LOXL2) were significantly overexpressed in KIRC at the level of mRNA expression, protein expression, and RCC cell lines. Further analysis demonstrated that higher mRNA expression ofLOXandLOXL2were significantly correlated with poor survival, tumor grade, individual cancer stages, and nodal metastasis status. DNA copy number amplifications and mRNA upregulation, DNA deep deletion, and mRNA upregulation were the main genetic mutations ofLOXandLOXL2, respectively. Prognostic analysis showed that the altered group had significantly poorer overall survival (OS) compared to the unaltered group (p = .0387). Co-expression analysis showedCP,PLOD2, andCOL5A1were significantly correlated withLOX, andCOL1A2was positively correlated withLOXL2. Further analysis confirmed that these co-expressed genes were significantly upregulated and predicted unfavorable prognosis in KIRC. Conclusion Multi-level analysis demonstrated thatLOXandLOXL2were significantly upregulated and predicted poor survival in KIRC, which may apply as promising biomarkers for diagnosis and therapy of KIRC in the future.