Negative density dependence (NDD) has been accepted as a key mechanism for biodiversity maintenance in natural forests and different lineages of natural enemies (fungus, bacterium, insect and virus) may be involved. Previous NDD related studies usually correlated seedling survival to the density of host-specific pests or pathogens along the distance to conspecific neighbors, and molecular defense responses of focal seedlings to natural enemies were seldomly concerned. By employing community functional genomics strategy, we extracted copy numbers of homologous genes in defense responses from transcriptomic data of 99 tree species and their inherent impacts on seedling survival were evaluated using partial linear regression analysis and general linear mixed-effects models. The community-level transcriptomic gene copy number of defense responses to fungus, insect and virus showed significant negative correlations with survival rates of the seedling community and the species-level gene copy number of defense response to insect significantly correlated with survival rates of top-twenty common seedling species. Moreover, presence of adult neighbors with distinct defense response to bacterial and viral pathogens survival of focal seedlings as predicted by NDD, while presence of seedling neighbors with similar defense response to insect tended to promote survival of focal seedlings which may be driven by insect-mediated biotic filtering or competitive exclusion. We conclude that both gene copy number and dissimilarities to adult and seedling neighbors in defense response to natural enemies determined seedling survival, indicating the critical contributions of molecular defense responses of plants to species coexistence and diversity maintenance in subtropical forests.