Magnetoelectric (ME) coupling effect of 2-2-type ferromagnetic/ferroelectric bi-layer multiferroic epitaxial thin film (La1.2Sr1.8Mn2O7/PbZr0.3Ti0.7O3, LSMO/PZT) on SrRuO3 (SRO) substrate is investigated systematically by using Landau–Ginzburg–Devonshire (LGD) thermodynamic theory and modified constitutive equations. The calculating results clarify the detail relationships between ME coupling response and the residual strain, the volume fraction of constituent phases, the interface coupling coefficients, the magnetic field and the temperature. It also shows that improved ME coupling response can be modulated by these parameters. External magnetic fields (H1) induced ME coupling effect could be enhanced around Curie Temperature (Tc) of ferromagnetic phase and ME voltage coefficient (αE31) approaches a maximum at H1∼4.5 kOe near Tc. The remarkable variations of ME coupling response can be used to provide useful guidelines on the design of multifunctional devices.