Nanotechnology is a rapid field of development with the enhancement of the production of different types of nanoparticles (NPs) applied in several industrial and commercial applications which increase the risk of their presence in the aquatic environment. Ag NPs have a wide application in everyday life products. However, there is concern about the exposure effects on aquatic organisms to these NPs. Therefore, this study aims to assess gene transcription alterations in mussels Mytilus galloprovincialis gills exposed for 2 weeks to Ag NPs (42 ± 10 nm, 10 µg.L(-1)). The genes were selected based on previous biomarkers and proteomic results and included superoxide dismutase (SOD), catalase (CAT), glutathione transferase (GST), caspase 3/7-1 (CAS), cathepsin L (CATH), heat-shock protein 70 (HSP 70), cytochrome P450 4YA (CYP 4YA), the elongation factor (EF1), actin and α- tubulin. No significant changes in gene transcription profiles were observed after exposure of M. galloprovincialis to Ag NPs for 15 days. The lack of significant gene transcription responses is in light with previous results obtained for mussels exposed to these NPs and may be related to the fact that enzyme kinetics and relative abundance of proteins (increase of antioxidant enzymes and metalllothioneins (MTs) with the time of exposure) do not always directly reflect their relative mRNA levels. Nevertheless, their overall expression maintenance may signify that, at end of the exposure period (15 days), the transcription of the respective genes is no longer required, pointing out to a possible adaptation effect to nanoparticles or due to the levels of Ag NPs accumulated in this tissue at this exposure time. This study highlights that gene transcription application and role as an additional and/or alternative end point approach is important to understand the mode of action of these emergent contaminants in aquatic organisms. However, in future studies, the time window needs to be adjusted, as genes are likely to respond earlier to the nanoparticle exposure.