A new analytical expression that directly relates the open-circuit voltage (Voc) in perovskite solar cells (PSCs) to the quasi-Fermi level splitting (QFLS), interface energy offsets, and nonradiative recombination losses has been derived. It is found that the QFLS of the active layer plays a dominant role in enhancing Voc of PSCs. The newly derived Voc is applied to two PSCs with the hole transport layer (HTL) of poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine], and poly(3-hexylthiophene-2,5-diyl) (P3HT) and found that the first PSC has a higher Voc, which agrees well with the experimental results. It is found that both PSCs exhibit saturation of Voc at the higher charge carrier generation rates and hence at higher light intensities. The lower Voc in PSC with P3HT as HTL is attributed to the stronger band bending and higher interfacial defects. In accordance with the results, a large quasi-Fermi level splitting and a minimal interfacial energy offsets may be considered when selecting material for high Voc PSCs.