Pain is a sensation that is difficult to remember. Pain exposure is a stimulus that can damage the development of the baby's brain and contribute to learning disorders and behavior in childhood. Therefore nursing intervention is needed that can reduce the pain response in infants, especially during hospital treatment. The aim of the study was to determine the effect of non-nutritive sucking (NNS) and ASI (Air Susu Ibu or Breast Milk) on oral responses to acute pain in the neonate when invasive actions were performed. The benefits of research as evidence-based practiced about administering NNS and ASI orally to pain responses in neonates when experiencing pain. The research design uses experimental nonequivalent control group before and after design. The population of all neonates admitted to Dr. Soekardjo Tasikmalaya, with a total sample of 30 respondents consisting of 15 ASI respondents and 15 respondents for the NNS group. Pain assessments instruments CRIES (Crying, Requiring an increase in oxygen, Increased vital sign, Expression, Sleeplessness) was applied. Data analysis used non parametric tests Mann Whitney and Wilcoxon. The results of the study showed no significant differences in pain response before and after the intervention (p-value 0.236). It was suggested that nurses can improve health education for parents to be able to provide breastfeeding during treatment, especially when the baby receives invasive action