The research studied the influence of matrix effect on the determination of lead concentration and isotope ratio through simulating blood matrix, and its correction by common analyte internal standardization (CAIS) method. The experiment results showed that CAIS method was suitable for the multi-element-matrix. The relative errors between the determined and the true concentration values are 20% (without correction), 8% (by conventional internal reference correction) and 2% (by CAIS correction), respectively. Otherwise, the influence of matrix effect and its correction for isotope ratio determination are not that obvious. Similarity of the mass number and properties between internal reference and analyte elements seems not important for CAIS correction, since very close correction results were obtained by using Tl and Dy as internal reference elements. Besides, correction results are not affected by different matrix dilution. Reliability and practicality of CAIS were proved by bovine blood standard material determination.