diff --git a/__tests__/application/response.test.js b/__tests__/application/response.test.js
index 94ea6945a..cd948655b 100644
--- a/__tests__/application/response.test.js
+++ b/__tests__/application/response.test.js
@@ -14,6 +14,7 @@ describe('app.response', () => {
   const app5 = new Koa()
   const app6 = new Koa()
   const app7 = new Koa()
+  const app8 = new Koa()
 
   it('should merge properties', () => {
     app1.use((ctx, next) => {
@@ -97,4 +98,17 @@ describe('app.response', () => {
       .expect('Transfer-Encoding', 'chunked')
       .expect(200)
   })
+
+  it('should not assign multiple content-type for response header', () => {
+    app8.use((ctx, next) => {
+      assert.throws(() => {
+        ctx.set('Content-Type', ['image/jpg', 'application/json'])
+      }, Error)
+      ctx.body = {}
+    })
+
+    return request(app8.callback())
+      .get('/')
+      .expect(200)
+  })
 })
diff --git a/lib/response.js b/lib/response.js
index 13769b997..b60b0baeb 100644
--- a/lib/response.js
+++ b/lib/response.js
@@ -510,6 +510,9 @@ module.exports = {
     if (this.headerSent || !field) return
 
     if (typeof field === 'string') {
+      if (field.toLowerCase() === 'content-type') {
+        assert(!Array.isArray(val), 'Assign multiple Content-Type for response header is not allowed')
+      }
       this.res.setHeader(field, val)
     } else {
       Object.keys(field).forEach(header => this.res.setHeader(header, field[header]))