A novel series of substituted pyrazolo-quinoline derivatives 7pa-7qg were synthesized efficiently by using molecular iodine in DMSO and further characterized based on 1H NMR, 13C NMR, IR and HRMS spectral studies. All the synthesized derivatives were screened for their in vitro cytotoxic activity against a panel of five different cancer cell lines such as A549, HeLa, SKNSH, HepG2 and MCF7. The compounds 7pc, 7pd, and 7pj exhibited considerable to promising anti-proliferative activity with IC50 values of 3.76, 3.87 and 3.83 µM against SKNSH cancer cell line. It was revealed that the compounds 7pa and 7pg have shown very close IC50 values of 2.43 and 6.01 µM, against A549 and MCF7 cancer cell lines respectively, which compared to positive control of Doxorubicin. This is the first report on the synthesis and in vitro anti-proliferative evaluation of pyrazolo-quinoline derivatives.