This research will conduct a study on the analysis of the Plasmodium falciparum molecule in Drug Resistance by identifying malaria as a case example. Malaria is an infectious disease that is still a problem in the health sciences in Indonesia. This research is first-year research with a draft proposal that has prepared. The research focused on ; (1) literature review to build a theoretical framework as a basis for conducting genetic analysis research on Plasmodium falciparum gene polymorphism against drug resistance (2) conducting studies and presenting accurate statistical data as background held research (3) conduct active and passive case detection with blood smear and blood spot sample in Purworejo district to found individu with P.falciparum infection and possibility of polymorphism gene of drug resistance(5). To assess prevalence and distribution of resistance genetic markers to Artemisinin and partner drugs in P.falciparum. The research uses qualitative and quantitative research methods We need to see that there needs to be a case study on malaria in Purworejo District as a district which is still profoundly affected by the disease. The team has the first hypothesis: (1) Purworejo districts are one area that has not yet escaped malaria cases (2) The level of malaria morbidity in Central Java province in 2016 there were around 2,190 cases (3) The research area is endemic areas with malaria cases has increased every year. Keywords: Molecular Analysis, Gene Polymorphism, Drug Resistance, Plasmodium falciparum