Ganoderma boninense, a soil-borne pathogenic fungus causing basal stem rot (BSR) disease in oil palm, is the major threat to cultivation in Southeast Asia, with the potential to reduce oil production by up to 80% in severely affected plantations. With a view to marker-assisted selection (MAS) of resistant planting material, we combined genetics and transcriptomics approaches to investigate the defense mechanisms of oil palm against infection by G. boninense. We first performed quantitative trait locus (QTL) mapping of BSR resistance using a multi-locus Bayesian variable selection approach applied to more than 10 years of data collected during pre-nursery tests of Deli and La Mé breeding populations. We found 6 and 5 BSR resistance loci segregating in Deli and La Mé respectively, with no overlap between them. Then we performed an RNA-sequencing approach on libraries of roots and bole of oil palm seedlings inoculated or not with G. boninense, focusing on Deli × La Mé crosses with contrasted BSR resistance. A Bayesian variable selection on predictors obtained by tracing the resistance loci haplotypes in profiled individuals identified 195 differentially expressed genes (DEGs) for the G. boninense inoculation × QTL interaction, among the 551 DEGs found for inoculation effects. The DEGs were located both in cis and trans positions compared to the segregating QTL intervals, enabling the prioritization of candidate genes and resistance mechanisms associated. Focusing on a strong effect QTL region on chromosome 4 in the Deli genetic background, we identified three candidate genes in cis positions that exhibited differential expression both in response to G. boninense inoculation and between resistant and susceptible haplotypes. Our study is the first combining QTL and RNA-seq approaches in oil palm based on genetically connected experimental setup, providing valuable information on the underlying mechanisms and paving the way for MAS of BSR resistant planting material.