Background: Numerous cellular processes are linked to the tumor necrosis factor alpha(TNF-α) superfamily and its corresponding receptors. Furthermore, a great deal of research has been done on their function in many pathogenic diseases, particularly in skin illnesses. The formation of acne lesions may be influenced by genetic variables that alter TNF-α expression. Objective: To assess TNF-α polymorphisms (-857 and -863) in Egyptian patients with acne vulgaris and their correlation to disease severity. Patients and methods: This study included 50 patients suffering from acne vulgaris of different severity (Patients group). In addition, 50 apparently healthy individuals of matched age and sex were chosen as a control group. They were recruited at random for one year duration from the outpatient clinic of Dermatology, Andrology and STD Department in Mansoura University Hospital. Results: Regarding TNF-α −857 polymorphism, CC was considered as the reference genotype and C was considered the reference allele. Our study revealed that AV cases were significantly associated with higher proportion of CT, CT+TT genotypes (p < 0.05 for each), with risk to develop AV (OR>1 for each). While, TT genotype in general and recessive models, as well as T allele were not associated with AV susceptibility. Regarding TNF-α −863 polymorphism, CC was considered as the reference genotype and C was considered the reference allele. Our study revealed that AV cases were significantly associated with higher proportion of AA, genotype, and A allele (p < 0.05 for each), with risk to develop AV (OR>1 for each). CA, CA+AA were not associated with AV susceptibility. Conclusion: We have demonstrated a statistically significant association between the TNF-α −857 and -683 single nucleotide polymorphism and the susceptibility to acne in Egyptian patients with acne vulgaris.