Background: Cisplatin is a potent anticancer drug, but its nephrotoxicity limits the clinical use of it. To reduce the Cisplatin-induced nephrotoxicity, various interventions have been implicated. The aim of this study was to examine whether preconditioning with normobaric hyperoxia would prevent Cisplatin-induced nephrotoxicity in patient with solid tumor. Methods: In a prospective study, 80 adult patients with solid tumor who were treated with Cisplatin between February 2011 and December 2011 were included. Forty-three patients were exposed to pure oxygen via non-rebreathing reservoir mask which increased the provided oxygen rate to 60% oxygen for 2 hours at 48, 24, and 6 hours before intravenous administration of Cisplatin and 37 patients received only Cisplatin as a control group. Estimated glomerular filtration rate (eGFR) calculated in all patients on day 1 before and on days 1, 3, 6, 30 after Cisplatin exposures. Results: Patients treated with Cisplatin and 60% oxygen showed a mild improvement in eGFR and mild reduction of serum creatinine after 30 days with statistically mild significant differences (p ¼ 0.048). Conclusion: This study showed that normobaric and intermittent precondition of 60% oxygen prior to Cisplatin treatment had an acute transient adverse effect on renal function; however, the improvement of renal function will be seen after 30 days. Thus, it may help to prevent Cisplatin nephrotoxicity.