Background <p>Childhood is a key period in promoting the foundations of a healthy development regarding physical, mental, and social health, therefore interventions for global wellbeing should aim at developing a good repertoire of life skills aimed at these areas. The goal of the present study was to test the effectiveness of a culturally sensitive Program for Life Skills Promotion for Children based on Cognitve Behavioral Therapy.</p> Methods <p>We conducted a quasi-experimental manipulation of two groups, in which we have randomly assigned participants (average 8 years old) to either an experimental (<i>N</i> = 40) or a wait list control (<i>N</i> = 34) group. An 11-session intervention was delivered to participants in a school context in small groups. After the intervention, participants were asked to complete a survey to assess their social skills, positive and negative affect, and symptoms of depression and anxiety.</p> Results <p>Participants in the intervention group showed healthier scores on the social skills rating scales of Assertiveness, Responsibility and Cooperation, and Empathy and Affection, and on the positive affect scale compared to the waitlist group. Higher scores of global anxiety were observed in the experimental condition compared to control in this highly vulnerable population.</p> Conclusions <p>A case was made for the relevance of life skills influence on children’s social, emotional, and interpersonal skills based on the PRHAVIDA-Children program, which focuses on teaching universal skills relevant for managing school and developmental challenges. More complex scenarios could complement this intervention with specific mental health modules to help children address context-specific challenges.</p>