Introduction: Gender-based violence is a worldwide problem. School-based socio-educational interventions could be effective in preventing gender-based violence. We assessed the effectiveness of the "Let's focus!" program, aimed at health and equitable interpersonal relationships among high school students. Methods: We conducted a quasi-experimental study in an intervention group (IG, n = 560) and a comparison group (CG, n = 366) of secondary school students in Terrassa, Spain between 2019 and 2021. Specifically, we performed an online questionnaire on sexism, acceptance of violence and machismo at baseline and after the intervention. We calculated multivariate linear regression models including satisfaction with the intervention, to evaluate the change in the variables' mean between CG and IG. Results: In comparison to the CG, in the IG hostile and benevolent sexism, and acceptance of violence decreased from baseline to after-intervention, in the group of participants highly satisfied with the intervention (42.4%); machismo did not vary. The multivariate regression analyses showed that the intervention was effective in reducing hostile sexism ([beta] = -6.40; CI95% (-11.92; -0.88)), benevolent sexism ([beta] = -5.57; CI95% (-10.52;-0.61)), and acceptance of violence ([beta] = -4.79; CI95% (-9.50; -0.09)) in highly satisfied students from the IG, in comparison to the ones from the CG, regardless of their age or gender. Discussion: Let's Focus! was effective in reducing sexism and decreasing acceptance of violence among students that were highly satisfied with the intervention.