Volatile organic compounds of plant origin can be used to develop biostimulants and plant-growth regulators. While screening volatile compounds from several plant species, safranal (2,6,6-trimethylcyclohexa-1,3-diene-1-carbaldehyde), an apocarotenoid produced by saffron (Crocus sativus L.), effectively enhanced primary root (PR) elongation in lettuce (Lactuca sativa L. cv. Legacy) seedlings. Therefore, we aimed to examine the effects of exogenous safranal treatment on the morphological and physiological characteristics of lettuce seedlings. The data showed that, three days after treatment with 19 mu mol/L safranal in the dark, lettuce seedlings showed a marked increase in PR length, whereas hypocotyl growth was suppressed. Based on transcriptomic and qRT-PCR analyses, a total of 114 gene expression alterations due to safranal application were detected, including upregulations of ethylene and abscisic acid (ABA) biosynthesis genes. Additionally, safranal promoted ethylene production in both roots and hypocotyls; however, AgNO3, an ethylene-signalling inhibitor, did not affect PR or hypocotyl length after safranal treatment. Safranal slightly increased root ABA content. Exogenous treatment with 1 mu mol/L fluridone (1-methyl-3-phenyl-5-[3-(trifluoromethyl)phenyl] pyridin-4(1 H)-one), a carotenoid-biosynthesis inhibitor, did not significantly affect safranal-induced changes in PR or hypocotyl length. Safranal alleviated NaCl (50 mmol/L)-induced inhibition of PR elongation and cell death in lettuce seedlings. Moreover, it mitigated the NaCl-induced increase in root O2- and H2O2 content. Altogether, our findings suggest that exogenous safranal regulated PR and hypocotyl lengths. These effects seemingly occur through mechanisms independent of ethylene, ABA, or reactive oxygen species. Safranal apparently alleviated salinity stress by reducing oxidative damage.