A new type of synthetic multi-element reference material (SyRM) with pseudo-biological matrix was prepared by a co-polymerization reaction of an aqueous solution of acrylamide and acrylic acid containing known amounts of the elements. SyRM has the excellent homogeneity and the quantitative retention of major and trace elements. Elemental composition can simulate the biological samples to be analyzed. SyRM can be used for the same purpose of conventional certified reference materials with high accuracy and precision. SyRM was applied as a comparative standard for non-destructive photon and α-particle activation analysis. Selective preconcentration methods combined with NAA were proposed and the SyRM containing about fifty elements with known amounts was prepared. In order to evaluate the reliability of present methods, 3d transition elements and rare earth elements were determined in the SyRM. It was clearly observed that these methods have good accuracy and precision in trace analysis of biological materials by comparing the analytical results with the original contents in the SyRM. The SyRM supported multielement analysis of marine macro-algae can be used as comparative standards for the quality assurance of analytical techniques.