Due to the overuse of antibiotics, people are worried that existing antibiotics will become ineffective against pathogens with the rapid rise of antibiotic-resistant strains. The use of cell wall lytic enzymes to destroy bacteria has become a viable alternative to avoid the crisis of antimicrobial resistance. In this paper, an improved method for cell wall lytic enzymes prediction was proposed and the amino acid composition (AAC), the dipeptide composition (DC), the position-specific score matrix auto-covariance (PSSM-AC), and the auto-covariance average chemical shift (acACS) were selected to predict the cell wall lytic enzymes with support vector machine (SVM). In order to overcome the imbalanced data classification problems and remove redundant or irrelevant features, the synthetic minority over-sampling technique (SMOTE) was used to balance the dataset. The F-score was used to select features. The Sn, Sp, MCC, and Acc were 99.35%, 99.02%, 0.98, and 99.19% with jackknife test using the optimized combination feature AAC+DC+acACS+PSSM-AC. The Sn, Sp, MCC, and Acc of cell wall lytic enzymes in our predictive model were higher than those in existing methods. This improved method may be helpful for protein function prediction.