Dental caries is a chronic, multifactorial disease and occurs by shifting of biofilm. Shifting of biofilm flora caused by poor oral hygiene, genetic factors, and long-term immune changes lead to an increase in Streptococcus mutans which results in decreased pH and demineralization on tooth surfaces. The body’s immune system serves to defend from foreign invaders. IFN-γ and lymphocytes are innate and adaptive immunity components that are responsible for the occurrence of disease. The role of the immune system becomes important in understanding the mechanisms of disease prevention. The effective function of the body’s immune system is to immediately eradicate the infectious agent from the body. The objective of this study was to analyze the expression of IFN-γ and salivary cell lymphocyte proliferation as an early detection marker of severe early childhood caries. Saliva taken from preschool-aged children 4 to 6 years was divided into two groups, ie heavy caries group with DMFT > 6 and caries-free with dmft = 0, for lymphocyte cell proliferation test using MTT assay and for expression test of IFN-γ using flow cytometry test. There are differences in lymphocyte cell proliferation and IFN-γ expression in the saliva of severe early childhood (S-ECC) caries and caries-free. The increase in lymphocyte proliferation and IFN-γ expression up to 6 hours incubation can be used as the indicator of early detection marker of severe early childhood caries.