As a potential oil producer, safflower (Carthamus tinctorius L.) is advisable for growing in marginal and dry areas. The scarcity of identified linked markers is a major restriction to successful breeding programs in safflower for unfavorable environments. The genetic enhancement of safflower is a prerequisite to improve its utility and acceptability as an oilseed crop. Thus, this study aimed to determine QTL monitoring the importance and determination of epistatic impacts and QTL inter loci interaction as well as QTL by interaction in the F9 population derived from a Mex 22-191/Goldasht safflower under normal and drought stress conditions in the growing season of 2019. A new linkage map with 69 polymorphic AFLP markers was made which covered 556 cM of the safflower genome. At last, 17 major QTL with additive impacts (A) and 66 epistatic QTL with additive × additive impacts (AA) for ten agronomic traits in different environments were determined. The additive and epistatic QTL described 3.04%-24.71% and 8.31%-56.5 %–24.71 % and 8.31 %–56.5 % of the phenotypic variations of traits, respectively. Seven main genomic regions on linkage group (LG) 4 and LG5 were co-localized QTL for various traits. QTL by interactions found that four additive QTL were included in AE, and ten epistatic QTL were involved in AAE impacts, indicating that stress vis-à-vis non-stress conditions responsible for QTL. The identity linked markers with main and stable QTL can be applied as information markers for future investigations to introduce the candidate markers for breeding programs in safflower to increase the effectiveness of selection or drought tolerance enhancement.