The Panzhihua mafic intrusion, which hosts a world-class Fe-Ti-V ore deposit, is in the western Emeishan region, SW China. The formation age (~260 Ma), and Sr and Nd isotopes indicate that the Panzhihua intrusion is part of the Emeishan large igneous province and has little crustal contamination. To assess ore genesis of the Panzhihua Fe-Ti-V ore deposit, two different models have been provided to explain the formation, namely silicate immiscibility and normal fractional crystallization. Silicate immiscibility occurring around 1,000°C at the late stage of basaltic magma evolution argues against the silicate immiscibility model. Apatite-hosted melt inclusion research indicates that silicate immiscibility occurred at the late stage of Panzhihua magma evolution, which may not have offered potential to form such large ore deposits as Panzhihua. Alternatively, continuous compositional variations of the Panzhihua intrusion and calculations using thermodynamic modelling software support the hypothesis that the Panzhihua deposit was formed by normal fractional crystallization. Reciprocal trace element patterns of the Panzhihua intrusion and nearby felsic rocks also coincide with the fractional crystallization model. Normal fractional crystallization of high-Ti basaltic magma played a key role in the formation of the Panzhihua Fe-Ti-V ore deposit.