The sea lamprey (Petromyzon marinus) is an invasive pest in the Laurentian Great Lakes. Current pest control programs for sea lamprey are expensive and can produce off-target effects. RNA interference (RNAi) based technologies have the potential to augment existing sea lamprey control programs. In this study, sea lamprey embryos and larvae (10-100 mm) were treated with small interfering RNAs (siRNAs) targeting housekeeping genes (β actin, α actinin, calmodulin, elongation factor 1α, splicing factor 1 and γ tubulin) and gene expression was measured. Three of the siRNA embryo treatments (α-actinin, calmodulin, splicing factor 1) produced significant knockdown and increased mortality while treatment with tubulin siRNA produced only knockdown. Larval siRNA treatments produced knockdown of four genes (α-actinin, calmodulin, elongation factor 1α, splicing factor 1) and increased mortality with tubulin-siRNA treatments. Differential effects of siRNA treatment across life stage and gene target are discussed. These results suggest that siRNAs have potential uses as species-specific pesticides in sea lamprey.