Situation of study (SoS) has been reported as an excellent strategy to promote students’ significant learning. This work intended to demonstrate how a SoS on health education (“Knowing cancer: a way to life”) can be implemented within the co-creation (CoC) framework. The study was carried out in a middle school, with the participation of five groups: students (14-15 years old), teachers, future teachers, university teacher trainers and health professionals. The 10 activities were carried out in school and outdoors for five months, undergoing a process of self-reflexive cycle: “reflecting and planning”, “acting and observing”, and “analyzing and reflecting”. Transcripts of debates and of students’ and teachers’ texts were subject to content analysis. This study on a topic of health education demonstrated that the Situation of Study implemented in a co-creation process was very efficient for students to develop significant learning.