Gene correction aims at repairing a defective gene directly in the cellular genome, which warrants tissue-specific and sustained expression of the repaired gene through its endogenous promoter. We have developed a novel system based on integrase-deficient lentiviral vectors (IDLVs) that allows us to correct an endogenous mutation using a strategy based on homologous recombination (HR). In a proof-of-concept approach, an IDLV encoding a repair template was co-delivered with an I-SceI nuclease expression vector to rescue a defective enhanced green fluorescent protein (EGFP) gene. Expression of the nuclease created a double-strand break within the target locus, which was crucial for stimulating IDLV-based gene repair. Stable gene correction was realized in up to 12% of the cells, depending on the vector dose, the nuclease expression levels, and the cell type. Genotypic analyses confirmed that gene correction was the result of genuine HR between the target locus and the IDLV repair template. This study presents IDLVs as valuable tools for introducing precise and permanent genetic modifications in human cells.