Protein tyrosine kinases (PTKs) are important components for signal pathways that control cell proliferation, differentiation and various regulatory mechanisms. Selective inhibition of the PTKs is now recognized as an attractive strategy for the development of new cancer therapeutics. Indolinone derivatives are already proved as potential PTK inhibitors of Fibroblast Growth Factor Receptor (FGFR) and anti cancer agent. In the present work, a set of indolinone derivatives are considered for chemometric designing for anti-cancer agents using ligand-based 3D QSAR and pharmacophore modelling studies. The 3D-QSAR models permit an understanding of steric, electrostatic, and hydrophobic along with HB acceptor and donor requirements for ligand interactions at the active site. Pharmacophore is the molecular framework that carries the essential features that can visualize the potential interaction between the ligand and the receptor and it is based on the kind of interactions observed in molecular recognition. In the present study, molecular field and similarity analyses (CoMFA: R2=0.997, Q2=0.714, se=0.037, R2pred=0.602, sp=0.351; CoMSIA: R2=0.999, Q2=0.747, se=0.016, R2pred=0.712, sp =0.541) explained that both steric and electrostatic are crucial for inhibitory activity. Additionally, HB acceptor and donor are obtained as important for HB bonding interactions. The pharmacophore modelling study (R2 = 0.924, Q2=0.752, se=0.047, R2pred=0.771, sp =0.421) revealed the importance of HB acceptor and donor for the binding interaction at the active site cavity along with ring aromatic feature is found to be prime factor for inhibitory activity of the molecules. The study explained that rings ‘C’ and ‘D’ along with carbon chain between them are found to be essential for inhibitory activity. The amine and oxo group present in the ring ‘C’ also found critical for bonding interactions in the active site cavity of tyrosin kinase.