We systematically studied the tissue tropism of H5N1 virus in a fatal human case, based on 24 autopsy tissue samples from 5 organ systems, and analyzed the relationship between viral load and host response level in selected tissues. We presented evidence suggesting that the H5N1 virus can infect selected tissue of selected 5 organ systems including respiratory, digestive, nervous, urinary and lymphoid system. High viral load can induce high proinflamatory factors level in tissues, and immune cells could be the target of the virus.