Sulfur trioxide (SO3) is a key precursor for the formation of secondary particulate matter in the atmosphere, and its emissions can lead to an increase in smog and the formation of acid rain. In order to meet the monitoring requirements of SO3 emissions from coal-fired power plants, this paper focuses on the optimization of SO3 gas measurement parameters based on tunable diode laser absorption spectroscopy (TDLAS). The spectral numerical simulation is performed using absorption spectral lines of SO3 near 7.323 μm. The interference of SO2 and H2O absorption spectra is suppressed by optimizing the measurement pressure parameter. Considering the chemical properties of SO3, the effect of temperature on the spectral absorbance of SO3 in the presence of H2O is comprehensively analyzed. The study finds that the system had good effects in suppressing interference and measuring SO3 spectral absorbance under 0.06 atm (1 atm=1.01×105 Pa) negative pressure and 340 ℃ heat tracing conditions. The results of this parameter optimization study have important theoretical reference significance for the development of SO3 gas measurement instruments and industrial field applications.