Aspergilli are filamentous fungi which can cause opportunistic infections in Acquired Immunodeficiency Syndrome (AIDS) patients. Aspergilli can be found in human tissues either in the form of spores or hyphae. p53 is a tumor suppressor gene located in the short arm of chromosome 17. It is a potent transcriptional regulator of genes which are involved in many cellular activities including cell cycle arrest, apoptosis and angiogenesis. A loss of tumor suppressor function of p53 is the most common event leading to the development of human cancers. The rate by which p53 has a homology between different species has been reported from human to other vertebrates, it has been reported that it is available within Drosophila melanogaster and C. elegans  . The aim of this study is to check if p53 is localized within Aspergilli or not using immunohistochemical techniques and study the relationship between Aspergilli infection and p53 in human lung tissues. 45 different samples of lung tissues, diagnosed as being none tumor, were taken randomly during the year of 2003-2004 from the autopsy cases submitted to the forensic medicine center in Irbid, Jordan. The sample group consisted of 12 females and 33 males. Labeled Streptavidin Biotin (LSAB) method and Mach-4 method were used to determine the Aspergilli infection and p53. The results show that the Aspergillus is presented in all used samples (100% of the infection) in the form of spores or hyphae and all infected samples have mutant p53 molecules (p53 was located in Aspergillus spores and hyphae). According to this study, it is safe to posit that the mutant p53 molecules may be used by Aspergillus for its multiplication. Seemingly it is a biological behavior of Aspergillus to produce p53. The fate of the p53 is questioned, is it going to interact with the human cells initiating cancer? Further experimental investigations are required to determine such pathway. In conclusion, this study shows that Aspergillus is a producing agent for p53 and Aspergillus pathogenicity is caused by production of p53.