Abstract: Since the cathode material of selenium hollow cathode lamps is a lead-selenium alloy, it can simultaneously excite characteristic spectral lines for both lead and selenium. When using atomic fluorescence spectrometry to determine selenium content in geological samples, interference from elevated lead levels in the matrix often causes varying degrees of positive bias. This leads to anomalously high peaks in selenium mapping results. Consequently, the selenium content in the aqueous sediment standard material GBW07379 could not be accurately determined due to this interference. The inability to determine lead content during selenium analysis renders this phenomenon highly concealed, and the difficulty in accurately measuring selenium levels negatively impacts data reliability. This study demonstrated that increasing the hydrochloric acid concentration in the sample solution to 40% and adding 1.0mL of ferric chloride solution can reduce lead interference within a limited range by altering the acidity of the sample solution and the amount of iron salt masking agent. By adding potassium ferricyanide as an oxidizing agent for lead, results indicate that less than 0.06% of lead in actual samples contributes to interference. Lead interference cannot be completely masked, and its interference with selenium is influenced by the combined effects of copper, lead, iron, and hydrochloric acid concentrations in the sample solution. A novel calibration method was established by simultaneously measuring the fluorescence values of selenium and lead through dual channels, enabling precise quantification of lead interference in each sample to obtain accurate selenium results. Inter-instrument comparisons validated the reliability of this method. Compared to existing approaches, this method eliminates the need to incorporate total lead content during calculations, enables real-time monitoring of lead interference on selenium, and mitigates the impact of matrix variations between samples on calibration.