The paralogous RNA helicases Ddx5 (p68) and Ddx17 (isoforms p72 and p82) are involved in many RNA metabolic processes , e.g ribosome biogenesis and transcriptional regulation. Here we used RNA interference and protein over expression to analyse specific effects of these DEAD box proteins on the expression of independently transcribed C/D-box snoRNAs U3, U8, and U13, which are essentially for modification and processing of ribosomal RNA. An influence on snoRNA promoter activities were determined by luciferase reporter assays in the presence and absence of a histone deacetylation inhibitor. We also examined the interaction of p68 with respective snoRNA promoter sequences by chromatin immunoprecipitation assays. We found that Ddx5 and Ddx17 negatively control the expression of U3-, U8- and U13-snoRNA whereas that of U14, an intron excised snoRNA and used as a control, was unaltered. We also show that p68 specifically interact with the genomic control regions of these snoRNAs in HeLa cells.