Bay scallops are commercially important bivalve species for fisheries and aquaculture in China, the USA, Peru and Chile, but their small size, short lifespan (<14 months) and serious inbreeding depression restrict the sustainable development of their aquaculture. Compared with bay scallops, some interspecific hybrids of bay scallops and Peruvian scallops exhibit longer lifespans and significantly larger sizes, which may result from the longevity genes of Peruvian scallops, which have lifespans of 7–10 years. The FoxO transcription factor integrates signals from different longevity-related pathways that play a crucial role in aging and longevity in terrestrial model organisms. However, limited information is available on its roles in the longevity of marine animals. Here, we extended this paradigm using Peruvian scallops and bay scallops, which have distinct lifespans. Cloning and sequence analysis of the FoxO ORFs (ApFoxO and AiFoxO) revealed 22 synonymous, 7 nonsynonymous SNPs and two InDels between the two species. The amino acid variations (Q27 and E28) near the AKT phosphorylation site (T21) may affect the activities of ApFoxO for longevity. Nutrient restriction could extend lifespan in terrestrial model organisms, and the expression of ApFoxO and AiFoxO both significantly increased under nutrient restriction, but the response in bay scallops was faster and more robust than that in Peruvian scallops. Furthermore, ionizing radiation caused significantly lower mortality and higher FoxO expression in Peruvian scallops. These results suggested that FoxO may play a protective role in longevity through nutrient availability and DNA repair for genomic stability. The significantly decreased expression of CAT and Mn-SOD and the increased β-GAL activity (a marker for senescence) after FoxO downregulation suggested that FoxO may contribute to longevity by controlling ROS with its antioxidase activity. The results of our work provide the basis for understanding the role of FoxO in longevity in scallops and its potential as a biomarker for selecting larger hybrids to benefit scallop aquaculture.