Cervical cancer is one of the most common types of cancer in women worldwide. In developed countries chemoresistance represents one of the major problems in treatment of cervical cancer. MicroRNAs (miRNA) are 18-21 nt long small RNAs first described by Ambros and colleagues in the model organism Caenorhabditis Elegans. Upon specifically binding target mRNAs, microRNAs have the ability to regulate physiological and pathophysiological cellular processes by modulation of gene expression. MiRNA-mRNA interaction leads to an inhibition of translation or degradation of the target mRNA, influencing mechanisms of canonical cellular pathways. Investigations of miRNA expression profiles have shown that miRNAs are representing useful biomarkers especially in cancer diagnosis through their cell and tissue specific expression profiles and experimental regulation of the expression of several miRNA candidates have been proven to influence cell homeostasis as well as pathophysiological processes. In order to prove the hypothesis that miRNAs are differentially regulated in cervical cancer cells under stress, and furthermore that miRNAs are acting as modulators for stress response of the cells and as drivers for development of chemoresistance respectively, a detection of the differential miRNA expression profile of a cellular model of cervical cancer with stepwise established chemoresistance was performed. Establishment of the miRNA expression profile by micro array analysis and further validation by PCR based methods as well as in silico analysis suggested potential key miRNA candidates. MiR-338-3p, miR-663, miR-4530, miR-381a and miR-495 were chosen for experimental upregulation by transfection in the cellular model of chemoresistant cervical cancer with subsequent investigation of its impact on cell cycle distribution, population doubling, cell migration and the underlying mechanisms for their contribution to chemoresistance. We observed that miRNAs are differentially expressed in cells with acquired chemoresistance. Moreover we investigated that transient transfection of miR-381 and miR-495 led to a marginal decrease of chemoresistance and the intracellular amount of ABCB1-mRNA, which was identified as a putative driver for acquired chemoresistance in our cellular model. Additionally a lentiviral based stable transfection of miR-338-3p reduced chemoresistance in the high- and low-resistant subclones. In addition, expression of ABCB1 was decreased on mRNA level as well as on protein level after experimental overexpression of miR-338-3p. Furthermore, in silico analysis identified the transcription factor cFOS as putative target of miR-338-3p, which showed partly reduced mRNA expression and reduced protein expression after stable transduction of miR-338-3p. We conclude that stably intracellular upregulation of miR-338-3p reduces the ability of chemoresistance by inhibition of ABCB1 expression via targeting cFOS, leading to a deregulation 9 of the transcription factor AP1. Our results indicate the potential ability of miR-338-3p for theapeutical application.