The Fe isotope ratios can be a useful tracer of geochemistry, biogeochemistry, and the environmental redox state. In this study, we investigated the feasibility of Fe isotopic analysis in Fe-dominated minerals by 193 nm excimer ns laser ablation combined with Nu Plasma 1700 high resolution MC-ICP-MS without matrix-match calibration. Several important instrument parameters were investigated, such as the effect of the addition of nitrogen gas and water vapor, the effects of analytical parameters such as ablation mode, laser fluence, pulse repetition rate, spot size on Fe isotopic mass bias during analysis were investigated as well. The results showed that the effects of ablation mode, spot size, laser pulse repetition rate, and line scan speed can be neglected, while laser fluence and matrix effects had significant influence on the Fe isotopic mass bias at dry plasma condition. These problems can be minimized using consistent lower fluence (1.5?3.5 J·cm-2), as well as the wet plasma conditions can significantly reduce the matrix effect in Fe isotopic analysis. Fortunately, with the water vapor and nitrogen gas addition after the ablation cell, an accurate and precise Fe isotope in pyrite, manganite, hematite, and chalcopyrite analysis by ns-LA-MC-ICP-MS can be achieved with non-matrix-matched calibration. The obtained accuracy and reproducibility of the in situ determinations of δ56FeIRMM-014 were both better than ± 0.10‰ (2 SD). This study indicated that there was a serious matrix effect in the Fe isotopic analysis of Fe-dominated minerals by ns- LA-MC-ICP-MS, and nitrogen gas mixed with water vapor-assisted ns- LA-MC-ICP-MS were an appealing option for the in situ Fe isotope analysis of Fe-dominated minerals with non-matrix-matched calibration.