Background: Preterm infants' caring is considered one of the most challenging and stressful events for mothers. Aim: To investigate the effect of educational intervention on preterm infant's mothers' knowledge regarding their caring skills and coping abilities. Subjects and Methods: A quasi-experimental (pre-post-test) research design was applied at the neonatal intensive care unit in Assiut University Children Hospital. Three tools were used: A structured interview questionnaire for the mothers, mothers' knowledge regarding their caring skills, and coping health inventory for parents scale. Results: The findings demonstrated that only 12 % of the studied mothers had good score of knowledge in pretest which increased significantly to 85% in posttest .Also, 61% of the mothers their coping abilities were adaptive in pretest increased significantly to 98% in posttest. Moreover, there was a statistically negative correlation between level of mothers' coping abilities and their total knowledge level regarding their caring skills in the pretest which was changed positively in posttest. Conclusion: The planned educational intervention would positively increase the mothers' knowledge about caring skills and would have adaptive coping abilities during the care of their preterm infants. Recommendations: Educational programs for mothers about caring for their preterm infants should be included in clinical routine care.