Abstract: The composition of irradiated nuclear fuel samples is complex, containing various fission products and actinide elements. The analysis of these nuclear reaction products is of great significance for basic research and engineering application. A method of high performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC-ICP-MS) was established for the analysis of actinide elements, stable and long half-life fission products in nuclear fuels to simplify the sample processing steps, improve analysis efficiency, reduce sample size and personnel exposure dose. To avoid using a dual column coupling system and adding ion pair reagents, a mixed mode chromatographic separation material was designed. Phenylethyl and sulfonic groups have good hydrophobic and cation exchange properties, respectively, achieving the separation of fission products and uranium on a single chromatographic column. The concentration and pH value of the eluent are two important factors affecting retention time. When the α-hydroxyisobutyric acid (HIBA) concentration is 400 mmol/L and the pH is 3.5-4.0, uranium flows out of the chromatographic column first, and increasing the pH can separate the lanthanide elements. The resolutions of uranium and lutetium, and between lanthanide elements are 3.8 and 2.2-7.6, respectively, achieving baseline separation. The interface connecting chromatography and mass spectrometry was designed, mainly including a proportional valve, a fraction collector, and a switching valve, and has functions such as independent and combined use of chromatography and mass spectrometry, flow control, mass spectrometry analysis, and component collection. The irradiated nuclear fuel core samples were analyzed, and chromatographic elution curves and partial semi-quantitative results of La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Y, Rb, Mo, Zr, Cs, U, Np, Pu were obtained. The method has the advantages of high efficiency, strong qualitative, quantitative and anti-interference ability, and can be used for isotope ratio and valence state analysis. This indicates that HPLC-ICP-MS using dual functional chromatography column has great potential in the rapid analysis of actinide elements, stable and long half-life fission products. Due to its qualitative identification and online monitoring capabilities for target components, this method can also be applied to the purification and preparation of small amounts of components in spent fuel and target materials.