使用EPPlus不需要创建文件，您可以使用流来完成所有操作，下面是一个ASP.NET ashx处理程序的示例，它将datatable导出到excel文件并将其服务回客户端：

public class GetExcel : IHttpHandler
  {
    public void ProcessRequest(HttpContext context)
    {
      var dt = DBServer.GetDataTable("select * from table");
      var ms = GetExcel.DataTableToExcelXlsx(dt, "Sheet1");
      ms.WriteTo(context.Response.OutputStream);
      context.Response.ContentType = "application/vnd.openxmlformats-officedocument.spreadsheetml.sheet";
      context.Response.AddHeader("Content-Disposition", "attachment;filename=EasyEditCmsGridData.xlsx");
      context.Response.StatusCode = 200;
      context.Response.End();   
    }

    public bool IsReusable
    {
      get
      {
        return false;
      }
    }

    public static MemoryStream DataTableToExcelXlsx(DataTable table, string sheetName)
    {
      var result = new MemoryStream();
      var pack = new ExcelPackage();
      var ws = pack.Workbook.Worksheets.Add(sheetName);

      int col = 1;
      int row = 1;
      foreach (DataRow rw in table.Rows)
      {
        foreach (DataColumn cl in table.Columns)
        {
          if (rw[cl.ColumnName] != DBNull.Value)
            ws.Cells[row, col].Value = rw[cl.ColumnName].ToString();
          col++;
        }
        row++;
        col = 1;
      }
      pack.SaveAs(result);
      return result;
    }
  }

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尝试使用此代码将数据导出到excel，可能会有帮助

public static void DataSetsToExcel(DataSet dataSet, string filepath)
{
    try
    {
        string connString = "Provider=Microsoft.ACE.OLEDB.12.0;Data Source=" + filepath + ";Extended Properties=Excel 12.0 Xml;";
        string tablename = "";
        DataTable dt = new DataTable();
        foreach (System.Data.DataTable dataTable in dataSet.Tables)
        {
            dt = dataTable;
            tablename = dataTable.TableName;
            using (OleDbConnection con = new OleDbConnection(connString))
            {
                con.Open();
                StringBuilder strSQL = new StringBuilder();
                strSQL.Append("CREATE TABLE ").Append("[" + tablename + "]");
                strSQL.Append("(");
                for (int i = 0; i < dt.Columns.Count; i++)
                {
                    strSQL.Append("[" + dt.Columns[i].ColumnName + "] text,");
                }
                strSQL = strSQL.Remove(strSQL.Length - 1, 1);
                strSQL.Append(")");

                OleDbCommand cmd = new OleDbCommand(strSQL.ToString(), con);
                cmd.ExecuteNonQuery();

                for (int i = 0; i < dt.Rows.Count; i++)
                {
                    strSQL.Clear();
                    StringBuilder strfield = new StringBuilder();
                    StringBuilder strvalue = new StringBuilder();
                    for (int j = 0; j < dt.Columns.Count; j++)
                    {
                        strfield.Append("[" + dt.Columns[j].ColumnName + "]");
                        strvalue.Append("'" + dt.Rows[i][j].ToString().Replace("'", "''") + "'");
                        if (j != dt.Columns.Count - 1)
                        {
                            strfield.Append(",");
                            strvalue.Append(",");
                        }
                        else
                        {
                        }
                    }
                    if (strvalue.ToString().Contains("<br/>"))
                    {
                        strvalue = strvalue.Replace("<br/>", Environment.NewLine);
                    }
                    cmd.CommandText = strSQL.Append(" insert into [" + tablename + "]( ")
                        .Append(strfield.ToString())
                        .Append(") values (").Append(strvalue).Append(")").ToString();
                    cmd.ExecuteNonQuery();
                }
                con.Close();
            }
        }
    }
    catch (Exception ex)
    {

    }
}

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更新：截至2023年11月10日，NPOI支持XLSX。

这个问题是在2023年3月5日提出的，确认XLSX支持的提交来自January 3, 2013。另一个证据是SO线程c# - Does NPOI have support to .xlsx format?。
侧记
NPOI在幕后使用微软的Open XML SDK for Office。