Microbial technology is an effective and low-cost way for the treatment of water contaminated with tetracycline. In this study, 6 strains were isolated form a piggery wastewater. Strain C4 with good performance of chemical oxygen demand (COD) degradation was shown to be the best effective in the experiment of 50 mg L−1 tetracycline removal. Strain C4 was identified as Bacillus cereus; it was immobilized with fungi Penicillium chrysogenum Y5 to construct the whole-cell immobilization system. The optimal combination conditions were shown that inactivated strain Y5 compared with the living one was better as the immobilization skeleton and the inoculated strain C4 at the logarithmic growth phase were more suitable. The combination pellets could obviously improve the percentage of COD degradation and tetracycline removal to 88% and 90%, respectively. Scanning electron microscope results confirmed that lots of strain C4 cells could successfully adsorbed on the surface of fungus. It can be found from Fourier transform infrared spectroscopy analysis that hydroxyl, carbonyl, carboxyl and amino groups are rich in the immobilization pellets and this would benefit the removal of tetracycline in the wastewater.