Box C/D small nucleolar RNAs (snoRNAs) are known to guide the 2^′‐O‐ribose methylation of nucleotides in eukaryotic ribosomal RNAs and small nuclear RNAs. Recently snoRNAs are predicted to regulate posttranscriptional modifications of pre‐mRNA. To expand understanding of the role of snoRNAs in control of gene expression, in this study we tested the ability of artificial box C/D RNAs to affect the maturation of target pre‐mRNA. We found that transfection of artificial box C/D snoRNA analogues directed to HSPA8 pre‐mRNAs into human cells induced suppression of the target mRNA expression in a time‐ and dose‐dependent manner. The artificial box C/D RNA directed to the branch point adenosine of the second intron, as well as the analogue directed to the last nucleotide of the second exon of the HSPA8 pre‐mRNA caused the most prominent influence on the level of HSPA8 mRNAs. Neither box D nor the ability to direct 2^′‐O‐methylation of nucleotides in target RNA was essential for the knockdown activity of artificial snoRNAs. Inasmuch as artificial box C/D RNAs decreased viability of transfected human cells, we propose that natural snoRNAs as well as their artificial analogues can influence the maturation of complementary pre‐mRNA and can be effective regulators of vital cellular processes.