Comprehensive non-targeted analysis of food products normally requires two complementary chromatographic runs to achieve maximum compound coverage. In this study, we present a sensitive tandem-LC method, which combines RP and HILIC separation in a single run. The setup consists of a C18 trap column and two subsequently coupled analytical columns (HILIC and C18) which are operated in parallel. First, hydrophobic compounds are retained on the RP trap column while rather hydrophilic compounds are directly transferred onto a HILIC phase. Next, the pre-fractionated sample composition is analyzed by HILIC or RP chromatography, respectively. The presented setup allows individual and independent gradient elution as well as interfacing with mass spectrometry. The performance of the method has been proven by means of food relevant standards and analysis of complex food samples (e.g. red wine, meat extract). The simple and robust setup provides high flexibility in the selection of column combinations and does not require sophisticated instrumental setups or software. The method significantly increases the covered polarity range compared to classical one-dimensional chromatography. Our results indicate that tandem LC is a valuable and universal tool in the non-targeted screening of various types of complex food samples.