Allotetraploid has the potential to become an important germplasm resource for genetic breeding of organisms. Previously, autotetraploid oysters have played a great role in the worldwide triploid oyster industry by mating with diploids to produce triploid seeds. However, whether allotetraploid oysters can be produced and their performance is unknown. Here, we carried out an artificial interspecific cross between tetraploid Crassostrea gigas and teraploid C. angulata, forming 4 experimental groups, two autotetraploid groups (GGGG: tetraploid C. gigas♀ × C. gigas♂, AAAA: C. angulata♀ × C. anguata♂) and two allotetraploid groups (GGAA: C. gigas♀ × C. anguata♂, AAGG: C. angulata♀ × C. gigas♂). These two pure tetraploid species hybridized without barrier to gamete reproductive isolation, resulting in high fertilization rate (>93%) and acceptable hatching rate (>78%). Reciprocal tetraploid hybrid survival rates were higher than that of pure tetraploids. Some degree of growth heterosis was observed, especially for yearlings. Mid-parent heterosis of wet weight and shell height at day 360 was 31.58% and 16.11%, respectively, which were primarily influenced by egg origin and mating strategy. Overall, the order of performance of the four groups in the warm water area was as following: AAGG>GGAA>AAAA>GGGG. Our results demonstrate that artificial interspecific hybridization between two tetraploid oysters can produce heterosis and that teraploid hybrids have the potential to become new genetic resources for the improvement of polyploid oysters.