X80 high-grade pipeline steel is the main material used in long-distance oil and gas transmission pipelines. During the application process, it was found that there was a significant difference in the toughness of the weld metal after welding steel plates from different manufacturers, which seriously affected the safety of oil and gas storage and transportation. There was an urgent need for a fast and accurate in-situ quantitative analysis method for the distribution of elements along the thickness direction of the weld seam to help explore the mechanism of the joint effect of X80 pipeline steel base material and welding material on the toughness of the weld metal. Therefore, this article proposed a method for in-situ quantitative analysis of Mn, Ni, Cr, Al, and Nb in weld using LA-ICP-MS. By optimizing the laser pulse frequency to 20Hz, laser energy to 100% (laser output mode Image Aperture), etching aperture to 100μm, and defocus distance 0μm, the strength and the stability of mass spectrometry signals were enhanced. The experiment was calibrated using standard samples matched with the matrix, and the matrix element⁵⁷Fe was used as the internal standard for correction. By analyzing related mass spectrometry interferences, isotopes²⁷Al, ⁵³Cr, ⁵⁵Mn, ⁶⁰Ni, and ⁹³Nb were selected. The established LA-ICP-MS micro zone in-situ quantitative analysis method was applied to analyze the distribution of element content in two X80 pipeline steel welds with the same welding material but different base material compositions. The correlation coefficient of this method ranged from 0.992 7 to 0.999 6, with a quantification limit of 0.23~2.57 μg·g^-1. The results showed that Mn, Cr, Al, and Nb with similar contents in the two base metals exhibited similar dilution at the root of the weld. In comparison, Ni elements with significant differences in content between the two base metals showed significant differences in content within 8.4 mm from the root of the weld. The impact test results showed that the toughness of weld with high Ni element content in the base material is relatively significantly higher. SEM analysis of weld root showed that the increase of Ni element content was conducive to forming lath bainite structure. Therefore, it is considered that the dilution of base metal to Ni in the root weld metal can be reduced by adding 0.14% Ni to X80 pipeline steel. The weld impact toughness can be improved by higher Ni content by promoting the low-temperature lath bainite transformation. The established LA-ICP-MS in-situ quantitative analysis method is of reference significance for ensuring the safe operation of the X80 long-distance pipeline.