To enhance the high-temperature oxidation performance of Ti-6Al-4V alloy, we successfully prepared a TiNiSiCrCoAl high-entropy alloy coating on its surface via laser cladding technology. X-ray diffraction, scanning electron microscopy, and electron probe microanalysis were used to characterize the microstructure, elemental distribution, and high-temperature oxidation resistance of the coating. The results indicated that the microstructure of the coating was composed of a matrix and a sigma phase. Owing to the rapid cooling via laser processing and the matched delta, delta H-mix, and omega, the matrix phase was an amorphous structure rich in Ti, Si, Cr, and Co, and the sigma phase was an FCC structure rich in Ti, Ni, Co, and Al. The volume fraction of the amorphous-structured matrix in the coating increased with increasing laser scanning speed. The section after the oxidation treatment was composed of an oxide layer, a transition layer, and a coating matrix. The oxide layer was composed of TiO2, Al2O3, and NiAl2O4, and the transition layer was rich in Si, Ni, and Co. The amorphous-structured matrix exhibited a higher oxidation resistance than the FCC-structured sigma phase. Compared with the Ti-6Al-4V substrate, the oxidation resistance of the coating increased by 10.7, 28.1, 40.5, and 65.1 times at different laser scanning speeds under oxidation at 800 C for 48 h, which indicates that the coating has better oxidation resistance than the Ti-6Al-4V alloy at high temperatures.