β-thalassemia (β-Thal) is a group of life-threatening blood disorders caused by either point mutations or deletions of nucleotides in β-globin gene (HBB). It is estimated that 4.5% of the population in the world carry β-Thal mutants (1), posing a persistent threat to public health. The generation of patient specific induced pluripotent stem cells (iPSCs) and subsequent correction of the disease-causing mutations offer an ideal therapeutic solution to this problem. However, homologous recombination-based gene correction in human iPS cells remains largely inefficient. Here, we describe a robust process combining efficient generation of integration-free β-Thal iPSCs from patients' cells and TALEN-based universal correction of HBB mutations in situ. We generated integration-free and gene-corrected iPSC lines from two patients carrying different types of homozygous mutations and showed that these iPSCs are pluripotent and have normal karyotype. We showed that the correction process did not generate TALEN induced off-targeting mutations by sequencing. More importantly, the gene-corrected β-Thal iPS cell lines from each patient can be induced to differentiate into hematopoietic progenitor cells (HPCs) and then further to erythroblasts expressing normal β-globin. Our studies provide an efficient and universal strategy to correct different types of β-globin mutations in β-Thal iPSCs for disease modeling and applications.