BACKGROUND: One half of adults who develop any mental disorder do so during adolescence. Previous literature showed that Mental Health Literacy (MHL) interventions impact mental health knowledge, reduce the associated stigma, and promote help-seeking among the adolescent population. However, evidence for the effectiveness and cost-effectiveness of these programmes remains inconclusive. The aim of this paper is to present a study protocol that evaluates the effectiveness of the " EspaiJove.net " programme. " EspaiJove.net " consists of a universal MHL intervention designed to promote mental health knowledge, increase help-seeking, reduce the stigma associated with mental illness, and prevent mental disorders in Spanish school settings. METHODS: A school-based clustered randomised controlled trial (cRCT) design with 12 months of follow-up. SUBJECTS: At least 408 secondary school students who attend the 3rd year of E.S.O (Compulsory secondary education for 13- to 14-year- olds) will be recruited from 8 schools within Barcelona city, Catalonia (Spain). INTERVENTION: A dose-response intervention will be delivered with 4 arms: 1) Sensitivity Programme (SP) in Mental Health (1 h); 2) Mental Health Literacy (MHL) Programme (6 h); 3) MHL plus first-person Stigma Reduction (MHL + SR) (7 h); 4) Control group: waiting list. Primary outcomes: 1) MHL: EspaiJove.net MHL Test (EMHLT); 2) Stigma: Reported and Intended Behaviour Scale (RIBS) and Community Attitudes toward the Mentally Ill (CAMI). Others outcomes: 1) Acceptability of intervention; 2) Mental health symptoms and emotional well-being (SDQ); 3) States of Change Scale (SCS); 4) Bullying and Cyberbullying; 5) Quality of life (EQ-5D); 6) Help seeking and use of treatment; 7) Health benefits. DISCUSSION: Results would be informative for efforts to prevent mental disorders and promote mental wellbeing in secondary school students.