Polycyclic aromatic hydrocarbons (PAHs) consist of a group of over 100 different organic compounds mainly generated by anthropogenic activities. Because of their low water solubility, they tend to be accumulated in sediment, where their degradation rate is very low. Few studies have been carried out so far to investigate the effects of PAHs on Artemia franciscana. Artemia is easy to manage at laboratory scale, but it is not a sensitive biological model considering the traditional endpoints (i.e., mortality). In addition to evaluating the lethality on nauplii and adults of A. franciscana after 24 and 48 h, we focused on the genotoxicity to investigate the potential effects of phenanthrene (PHE), naphthalene (NAP), fluoranthene (FLT), and benzo(k)fluoranthene (BkF). Results showed that FLT was the most toxic both for nauplii and adults after 48 h of exposure. Real-time qPCR showed that all toxicants, including BkF, which had no negative effects on the survival of the crustacean, were able to switch the gene expression of all nine genes. This work has important ecological implications, especially on contaminated sediment assessment considering that PAHs represent the most abundant organic group of compounds in marine environment, opening new perspectives in understanding the molecular pathways activated by crustaceans.