diff --git a/js/web/lib/wasm/jsep/init.ts b/js/web/lib/wasm/jsep/init.ts
index 93d390dd64..dd875cda12 100644
--- a/js/web/lib/wasm/jsep/init.ts
+++ b/js/web/lib/wasm/jsep/init.ts
@@ -98,6 +98,10 @@ class ComputeContextImpl implements ComputeContext {
 export const init = async(module: OrtWasmModule, env: Env): Promise<void> => {
   const init = module.jsepInit;
   if (init && navigator.gpu) {
+    if (!env.wasm.simd) {
+      throw new Error(
+          'Not supported for WebGPU=ON and SIMD=OFF. Please set `env.wasm.simd` to true when using WebGPU EP');
+    }
     const backend = new WebGpuBackend();
     await backend.initialize(env);