Background <p>Understanding the emergence and spread of anti-malarial resistance, particularly to artemisinin and its partner drugs, is essential for eradicating malaria in worldwide. To identify genetic markers associated with susceptibility to common anti-malarial drugs, the in vitro sensitivities of anti-malarial drugs were evaluated, and a genome-wide association study of&#xa0;<i>Plasmodium falciparum</i>&#xa0;susceptibility in vitro to multiple anti-malarial drugs was conducted.</p> Methods <p>Genomic DNA from 34 samples of <i>P. falciparum</i> collected between 2007 and 2010 in the Nabang-Lazan Valley along the China-Myanmar border was extracted and subjected to whole-genome sequencing. The standard SYBR Green I-based fluorescence assay and RSA assay were used to evaluated the in vitro sensitivities of anti-malarial drugs. Plink v1.90 was used to investigate the associations of genome-wide SNP with in vitro sensitivities to anti-malarial drugs.</p> Results <p>The proportion of isolates showed reduced-susceptible to CQ,SP,QN,PPQ and PND were 88.24%,92.59%,8.82%,8.82%,5.88%, respectively. 93.54% of isolates showed high level of the IC₅₀ values of CQ have a <i>pfcrt</i> CIETS mutations. The isolates with <i>pfdhfr</i> IRNI, NRNL and IRNL mutations showed high SP IC₅₀ values. SNPs on <i>pfhsp90</i> and <i>pfevp1</i> showed significant association with IC₅₀ values of CQ. Of particular interest is the significant association found between a locus on chromosome 13 and the sensitivity to dihydroartemisinin. This locus is situated within the gene encoding the inner membrane complex protein 1F (<i>IMC1F</i>),which has been found to be associated with the <i>kelch13</i> compartment in schizont stages of <i>P. falciparum.</i></p> Conclusions <p>Multiple genetic markers correlating with anti-malarial drug susceptibility were identified in the study, which provide a reference for further investigations into the association between oxidative stress-mediated activity and anti-malarial drugs susceptibility.</p>