Drug-target prediction method can effectively reduce costs and accelerate research process compared with traditional drug discovery. However, there are various challenges such as low balance of datasets and low precision of prediction in practical applications. Therefore, a drug-target interaction prediction method based on self-adaptive spherical evolution was proposed, namely ASE-KELM (self-Adaptive Spherical Evolution based on Kernel Extreme Learning Machine). By the method, negative samples with high confidence were selected based on the principle that drugs with similar structures are likely to interact with targets. And to solve the problem that spherical evolution algorithm tends to fall into local optima, the feedback mechanism of historical memory of search factors and Linear Population Size Reduction (LPSR) were used to balance global and local search, which improved the optimization ability of the algorithm. Then the parameters of Kernel Extreme Learning Machine (KELM) were optimized by the self-adaptive spherical evolution algorithm. ASE-KELM was compared with algorithms such as NetLapRLS (Network Laplacian Regularized Least Square) and BLM-NII (Bipartite Local Model with Neighbor-based Interaction profile Inferring) on gold standard based datasets to verify the performance of the algorithms. Experimental results show that ASE-KELM outperforms comparison algorithms in AUC (Area Under the receiver operating Characteristic curve) and AUPR (Area Under the Precision-Recall curve) for the Enzyme (E), G-Protein-Coupled Receptor (GPCR), Ion Channel (IC), and Nuclear Receptor (NR) datasets. And the effectiveness of ASE-KELM in predicting new drug-target pairs was validated on databases such as DrugBank.