Integration of microfluidics and optical components is an essential requirement for the realization of optical detection in lab-on-a-chip (LOC). In this work, a novel hybrid integration of silica-on-silicon (SOS) waveguide and polydymethylsiloxane (PDMS) microfluidics for realizing optical detection based biochip is demonstrated. SOS is a commonly used platform for integrated photonic circuits due to its lower absorption coefficient of silica and the availability of advanced microfabrication technologies for fabricating complicated optical components. However, the fabrication of complex microfluidics circuits on SOS is an expensive process. On the other hand, any complex 3D and high-aspect-ratio microstructures for the microfluidic applications can be easily patterned on PDMS using soft lithography. By exploring the advantages of these two materials, the proposed hybrid integration method greatly simplifies the fabrication of optical LOC. Two simple technologies—namely, diamond machining and soft lithography—were employed for the integration of an optical microfluidic system. Use of PDMS for the fabrication of any complex 3D microfluidics structures, together with the integration of low loss silica-on-silicon photonic waveguides with a straight microfluidic channel, opens up new possibilities to produce low-cost biochips. The performance of SOS-PDMS-integrated hybrid biochip is demonstrated with the detection of laser induced fluorescence of quantum dots. As quantum dots have immense application potential for biodetection, they are used for the demonstration of biodetection.