BackgroundThe purpose of the study was to recognize the social representation of the Guna indigenous population by identifying cultural elements related to malaria, in order to create an intercultural approach to any health intervention to control and prevent the disease.MethodsThis qualitative study has an anthropological focus that used participant observation, informal conversations, focus groups, interviews, in-depth interviews with key actors. Analyses included review, classification and categorization of interviews.ResultsMalaria within the Guna culture is in harmony with several cultural factors, such as magic, religion, beliefs, myths, and nature. The health system must include these factors in its intercultural approach to ensure the sustainability of anti-malarial intervention measures. Until this is not properly addressed, the Guna population of Madungandi will remain a permanent source of risk for malaria transmission in this region and for the rest of the country.ConclusionThe findings of this study contribute new variables that can facilitate an intercultural approach to improve the perception of malaria in the indigenous population of Comarca Guna de Madungandi, Panama.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1899-4) contains supplementary material, which is available to authorized users.