Powdery mildew disease caused by Golovinomyces cichoracearum is one of the most important diseases of cucumber that cause quality and quantity damage in many parts of Iran. With regular and proper use of appropriate and effective fungicides can be significantly reduced as much as economic losses due to this disease. To study the efficacy of new fungicide, azoxystrobin + difenoconazole (Safir® SC 32.5% and Diforobin SC 32.5%) in controlling cucumber powdery mildew disease, experiments were carried out in Alborz, Tehran, and Khuzestan provinces in a Randomized Complete Block Design (RCBD) with 9 treatments and 4 replications under glasshouse conditions. Treatments included 0.5, 0.6 and 0.75 ml/L-1 of Safir®, 0.5, 0.75 and 1 ml/L-1 of Diforobin and tetraconazol (Domark® EC 10%) 0.4 ml/L-1, bicarbonate potassium (Kaliban® SL 85%) 5 gL-1 along with control without any spraying. Foliar applications of fungicides started once after early symptoms appearance and followed up at 5-14 days intervals. The results were expressed before each spraying and 14 days after last spraying as the disease severity index (DSI). Disease severity was classified from 0-7 using the Horsfall and Barrat scale. Mid-point of disease severity calculated using the Horsfall and Barrat scale for each plant. Development of the Area Under the Disease Progressive Curve (AUDPC) calculated by using all samplings data at disease cycle period. All samplings data, AUDPC were analyzed by SAS software and means compared using Duncan multiple range tests (P = 5%). As the analysis of variance (ANOVA) indicated significant difference resulted from interaction between fungicide treatments and location, so the analysis of variance (ANOVA) made for each location as a separate case too. The efficacy comparisons revealed that Safir® 0.75 ml/L-1, Diforobin® 0.75 and 1 ml/L-1 and Domark® 0.4 ml/L-1 as a standard treatment had the same effects due to statistical points and decreased the Area Under the Disease Curve by the 90% compared to unsprayed check treatment. These comparisions also showed that the fungicides Safir® and Diforobin® at the rate of 0.5 ml/L-1 had more than 70% efficacy. The Kaliban® 5 g/L-1 as a mineral standard fungicide decreased the AUDPC more than 50% compared to unsprayed check treatment had the lowest efficacy amoung treatments. Based on the results gained from this research, the fungicides Safir® and Diforobin® may be recommended to be used for registration at 0.75 ml/L-1 for 7 to 14-days intervals.