The aim of this study was to develop a liquid chromatography/tandem mass spectrometry LC-MS/MS method for the simultaneous determination of acrylamide and hydroxymethylfurfural (HMF) in corn snack products enriched with food industry by-products: brewer’s spent grain (BSG), sugar beet pulp (SBP) and apple pomace (AP). Development of the method included the study of different sources for ionization, different mobile phases, different extraction conditions as well as different methods of sample preparation. Finally, the single LC-MS/MS method was developed for the analysis of both analytes in one step with a duration of 20 min using a simple single-step extraction. The method with apparent recoveries of 91.4 and 90.4 for acrylamide and HMF, respectively, was applied for the analysis of non-extruded and extruded samples. The obtained results shown that the acrylamide content was <LOD (limit of detection) for all raw materials and non-extruded mixtures, while HMF increased proportionally to the content of added by-products in the mixtures. After the extrusion process, quantification of the acrylamide could be done in all samples. A higher amount of by-products entails higher contents of acrylamide and HMF, with the most significant effect in AP extrudates, where the highest content of HMF (6069 ± 789 ng/g) and acrylamide (5.37 ± 0.50 ng/g) in samples with 15% AP was observed.