We investigated the binding interactions of a porphyrin derivative (TMPyP4) with two antiparallel basket-type human telomeric quadruplexes under K+ ion conditions by molecular dynamics simulations. Nine quadruplex TMPyP4 complexes each with a 1:1 stoichiometry were built for every quadruplex, including the binding modes of end stacking, intercalation, external groove binding, and external loop stacking. Detailed structures analysis, free energy calculations, and principal components analysis were performed. The results show that the end stacking mode is the best binding mode, with high binding affinity and high stability of quadruplexes, and next is the external loop stacking mode, with relatively high binding affinity and high stability of quadruplexes. The groove binding mode has the relatively low binding affinity, and the quadruplexes are stabilized well. The intercalation mode has very high binding affinity, but the quadruplexes are not stabilized and show very high flexibility.