Introduction: Malaria remains today the most frequent parasitic disease on the planet with, in 2021, 247 million cases and 619,000 deaths worldwide. Its control is compromised by the spread of the parasite's resistance to available antimalarials. The objective of our study is the characterization of Plasmodium falciparum resistance genes to common antimalarial drugs in semi-urban areas of Burkina Faso.Material and Methods: This is a prospective cross-sectional study whose collection took place from June to October 2021 and from June to October 2022 in ve health facilities in Burkina Faso. The molecular analysis took place from January to June 2023 at Centre National de Recherche et de Formation (CNRFP) to determine resistance genes such as Pfcrt, Pfmdr1, Pfdhps, and Pfdhfr. We have used the PCR-RFLP technique.Results: On 150 samples analyzed we obtained prevalence of 46.67 %, 1.33 %, 0.67 %, 20%, 82%, and 4.67%, respectively for the mutations Pfcrt76T, Pfmdr1 86Y, Pfdhps 437G, Pfdhfr 51I, Pfdhfr 59R, and Pfdhfr 108N. There are no mutations observed for the mutant strains Pfdhps 540E and Pfdhfr 164L. However, the mutant strain Pfdhfr 59R was the most found and we also observed in general a triple mutation (Pfdhps 437G + Pfdhfr 59R + Pfdhfr 108N) with a low frequency which is 0.67%. Conclusion: It would be wise to carry out increased surveillance of Plasmodium falciparum resistance markers to antimalarial drugs, one of the priorities in the context of the control or malaria elimination.