When species are translocated to a novel environment, individuals become exposed to new predators against which they may not express very efficient defences at least at an initial stage. The strength of anti-predator defence is an important parameter that may determine the ability of local communities to control the expansion of invasive populations. The African clawed frog, Xenopus laevis, is a globally invasive amphibian that has successfully established invasive populations on four continents. In its invasive distribution in western France, X. laevis encounters novel aquatic predators. Some may be related to the predators in the native range but others may belong to different taxonomic groups and not be functionally or ecologically equivalent. We tested whether naïve X. laevis tadpoles from the invasive French population exhibit anti-predator response to local predators, and whether the response depends on the degree of relatedness with predators encountered in the native range of the frog, or whether individuals may express generic neophobia to any cue they are not familiar with. We exposed naïve lab-reared tadpoles to a native non-predatory water snail, Planorbarius corneus, a native predatory beetle, Dytiscus dimidiatus, and an invasive predatory crayfish, Procambarus clarkii. We found that X. laevis tadpoles innately reduce their activity when exposed to beetle and crayfish stimulus cues, but not to snails. Reducing activity can decrease the probability of being detected by predators. This demonstrates that invasive tadpoles respond to known and novel predators regardless of the evolutionary history. Whether the produced response is always effective against a totally novel predator remains to be tested.