Background: Early childhood caries is a biofilm-dependent, critical, widespread health problem in both developing and industrialized countries. The interleukin-6 (IL-6) has several roles in the body's response to inflammation and tissue damage. TNF-α is a pleiotropic cytokine that acts as a pro-inflammatory cytokine. Aim of Study: The purpose of this research was to assess the salivary concentrations of TNF-α and IL-6 in children with dental caries and study the correlation between cytokines and DMFs index. Materials and Methods: Eighty children aged four and five took part in the study. Forty children with ECC served as the research group, whereas 40 caries-free children of the same age and gender served as the control group. Clinical parameters were assessed after an oral examination and measurement. All participants had saliva samples obtained. IL-6 and TNF-α concentrations in saliva were estimated using an ELISA test. Results: The current study found a significant elevation (P<0.05) in mean levels of TNF-α and IL-6 among children with ECC in comparison to caries free children. Moreover, there is significant positive correlation between IL-6 and TNF-α levels in caries children. Conclusion: Based on these results, it seems likely that elevated levels of TNF-α and IL-6 are involved in ECC.