The purpose of this study is the development and validation of a simple, novel, selective and fast off-line microextraction technique combining capillary electrophoresis with in-column field-amplified sample injection (FASI) for the simultaneous determination of capecitabine (CAP) and its active metabolite, 5-Fluorouracil (5-FU), in human plasma. At the moment, there is a lack of using cost-effective CE tool combined with novel miniaturized sample clean-up techniques for analysis of these important anticancer agents in plasma samples. This paper intends to fill this gap and describe a simple off-line sample pretreatment by means of AgNPs@MCM-41 reinforced hollow fiber Solid/Liquid phase microextraction (AgNPs@MCM41-HF-SLPME) with subsequent quantitation by FASI-CE. The separation of analytes was performed using a BGE containing 60 mM phosphate-Tris buffer (pH 7) with 10% methanol as an organic modifier. Before sample loading, a short water plug (50 mbar, 3 s) was injected to permit FASI for stacking. Various parameters affecting the off-line microextraction efficiency as well as FASI were optimized. Migration time was found to be 6.6 (+/- 0.1) min for 5-FU and 7.4 (+/- 0.2) min for CAP. The linearity, precision, accuracy, recovery, selectivity, specificity, stability as well as the robustness of the method was evaluated from spiked plasma samples during the course of validation. The results revealed that the presented technique demonstrates acceptable accuracy and precision, miniaturized sample preparation and a reduced need for complicated equipment along with an acceptable analysis time. The validated method was successfully applied to determine CAP and 5-FU in patient's plasma samples. (C) 2016 Elsevier B.V. All rights reserved.