Yes, its possible, if you want to change something inside file, you have to open it using code and start working on it, OpenXML SDK will help you to achieve this.
Step1: Install nuget package - DocumentFormat.OpenXml 2.5.0.
Step2: Modify your code
protected void btnUpload_Click(object sender, EventArgs e)
{
string fileName = Path.GetFileName(FileUpload1.PostedFile.FileName);
FileUpload1.PostedFile.SaveAs(Server.MapPath("~/") + fileName);
fileName = Server.MapPath("~/") + fileName;
using (var document = WordprocessingDocument.Open(fileName, true))
{
RunProperties runProp = new RunProperties();
RunFonts runFont = new RunFonts();
runFont.Ascii = "Arial";
DocumentFormat.OpenXml.Wordprocessing.FontSize size = new DocumentFormat.OpenXml.Wordprocessing.FontSize();
size.Val = new StringValue("48");
runProp.Append(runFont);
runProp.Append(size);
Run r = document.MainDocumentPart.Document.Descendants<Run>().First();
r.PrependChild<RunProperties>(runProp);
document.MainDocumentPart.Document.Save();
}